(9H-Fluoren-9-yl)methyl decyl(2-oxoethyl)carbamate

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of oxalyl chloride (12.24 mL) and methylene chloride (50 mL) at −35 to −45° C. was added DMSO (14.75 g) in methylene chloride (25 mL) over 20 minutes. The reaction mixture was stirred for 10 minutes at −35 to −45° C. A solution of N-Fmoc-2-(n-decylamino)ethanol (20.0 g) in methylene chloride (70 mL) was added over 25 minutes and then stirred 40 minutes at −35 to −45° C. Triethylamine (21.49 g) was then added and the mixture stirred for 30 minutes at −10 to −20° C. The reaction mixture was quenched with water (120 mL) followed by concentrated sulfuric acid (20.0 g) while maintaining the internal temperature at 0-5° C. The organic layer was isolated and washed with 2% sulfuric acid (100 mL) followed by water (2×100 mL). The organic solution was distilled under vacuum at 60° C. to about 100 mL. Heptane (100 mL) was added, the temperature of the oil bath raised to 80° C. and the distillation was continued until the residual volume was 100 mL. More heptane (100 mL) was added and the distillation repeated to a volume of 100 mL. The heating bath was replaced with a cold water bath at 15° C. The bath was cooled slowly to 5° C. over 20 minutes to start the precipitation of the product. The slurry was then cooled to −5 to −10° C. and the slurry was stirred for 2 hours. The solid was then collected on a Buchner funnel and washed with cold (−5° C.) heptane (2×15 mL). The wet solid was dried in vacuo to yield the title aldehyde. stirred 40 minutes at −35 to −45° C the mixture stirred for 30 minutes at −10 to −20° C The reaction mixture was quenched with water (120 mL) while maintaining the internal temperature at 0-5° C The organic layer was isolated washed with 2% sulfuric acid (100 mL) The organic solution was distilled under vacuum at 60° C. to about 100 mL Heptane (100 mL) was added the temperature of the oil bath raised to 80° C. the distillation More heptane (100 mL) was added the distillation The heating bath was replaced with a cold water bath at 15° C The bath was cooled slowly to 5° C. over 20 minutes the precipitation of the product The slurry was then cooled to −5 to −10° C. the slurry was stirred for 2 hours The solid was then collected on a Buchner funnel washed with cold (−5° C.) heptane (2×15 mL) The wet solid was dried in vacuo

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A three-necked, 500 mL round bottom flask equipped with a thermometer, mechanic stirrer and an addition funnel was purged with nitrogen and charged with N-allyldecylamine (˜0.11 mol) in dichloromethane from step a (210 mL) and N,N-diisopropylethylamine (20.0 mL, 14.8 g, 0.113 mol). The mixture was cooled in a 5° C. ice bath and a solution of 9-fluorenylmethyl chloroformate (25.6 g, 0.099 mol) dissolved in dichloromethane (50 mL) was added dropwise (total volume approximately 330 mL). The reaction was exothermic and the internal temperature was controlled below 10° C. throughout the 9-fluorenylmethyl chloroformate addition. The reaction mixture was warmed to 21° C. when the addition was finished, and monitored by the disappearance of 9-fluorenylmethyl chloroformate and the formation of N-FMOC-N-allyldecylamine using HPLC (retention time for FMOC-chloride=3.08 min; retention time for product=7.96 min). The reaction mixture was washed with 0.01 N HCl (100 mL). The organic layer was collected and used without further purification. A three-necked, 500 mL round bottom flask equipped with a thermometer, mechanic stirrer and an addition funnel was purged with nitrogen was added dropwise (total volume approximately 330 mL) The reaction mixture was warmed to 21° C. when the addition The reaction mixture was washed with 0.01 N HCl (100 mL) The organic layer was collected used without further purification

Conditions: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A three-necked, 1000 mL round bottom flask equipped with a magnetic stir bar and a gas inlet tubing was charged with N-FMOC-N-allyldecylamine (˜0.099 mol) in dichloromethane (280 mL) and methanol (50 mL). The mixture was cooled in a −65° C. dry ice-chloroform bath and purged with a stream of dilute ozone in oxygen for 2.5 hours (internal temperature about −55° C.; flow rate for dilute ozone in oxygen about 1.0 L/min). The reaction was monitored by HPLC (retention time for starting material=7.96 min; retention time for product=5.82 min). Upon disappearance of the allyl starting material, ozone purging was discontinued and the mixture was purged with nitrogen for 20 minutes to remove excess ozone. The reaction mixture was then treated with triethylamine (24.8 mL, 0.178 mol) at −55° C., warmed to 21° C., and stirred for 3 hours. The reaction mixture was washed with water (50 mL); 0.01 N HCl (50 mL) and the organic layer was concentrated in vacuo to give an oil. Heptane (150 mL) was added and the mixture was concentrated in vacuo to azeotropically remove water and dichloromethane. This azeotropic procedure was repeated two more times using heptane (150 mL) to give a final volume of about 100 mL. The resulting organic solution was charged to a 200 mL three-necked round bottom flask and cooled to 15° C. in a water bath. Pieces of ice were added slowly to the water bath to cool the mixture to 5° C. in a period of 40 minutes (the mixture was seeded at approximately 10° C.). The cloudy mixture was further cooled to −10° C. and stirred for 2.5 hours. The resulting suspension was filtered through a Buchner funnel and the precipitate was washed with ice cold heptane (20 mL×2). The precipitate was collected and dried in vacuo (25 mmHg) for 6 hours to give N-FMOC-2-(n-decylamino)acetaldehyde (25.6 g; 61% yield; 99% purity) as a white waxy powder. A three-necked, 1000 mL round bottom flask equipped with a magnetic stir bar and a gas inlet tubing purged with a stream of dilute ozone in oxygen for 2.5 hours (internal temperature about −55° C.; flow rate for dilute ozone in oxygen about 1.0 L/min) was monitored by HPLC (retention time for starting material=7.96 min; retention time for product=5.82 min) the mixture was purged with nitrogen for 20 minutes to remove excess ozone warmed to 21° C. The reaction mixture was washed with water (50 mL) 0.01 N HCl (50 mL) and the organic layer was concentrated in vacuo to give an oil the mixture was concentrated in vacuo to azeotropically remove water and dichloromethane to give a final volume of about 100 mL The resulting organic solution was charged to a 200 mL three-necked round bottom flask cooled to 15° C. in a water bath to cool the mixture to 5° C. in a period of 40 minutes (the mixture was seeded at approximately 10° C. The cloudy mixture was further cooled to −10° C. stirred for 2.5 hours The resulting suspension was filtered through a Buchner funnel the precipitate was washed with ice cold heptane (20 mL×2) The precipitate was collected dried in vacuo (25 mmHg) for 6 hours

Conditions: temp:-65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A three-necked, 1000 mL round bottom flask equipped with a magnetic stir bar and a gas inlet tubing was charged with N-FMOC-N-allyldecylamine (˜0.099 mol) in dichloromethane (280 mL) and methanol (50 mL). The mixture was cooled in a −65° C. dry ice-chloroform bath and purged with a stream of dilute ozone in oxygen for 2.5 hours (internal temperature about −55° C.; flow rate for dilute ozone in oxygen about 1.0 L/min). The reaction was monitored by HPLC (retention time for starting material=7.96 min; retention time for product=5.82 min). Upon disappearance of the allyl starting material, ozone purging was discontinued and the mixture was purged with nitrogen for 20 minutes to remove excess ozone. The reaction mixture was then treated with triethylamine (24.8 mL, 0.178 mol) at −55° C., warmed to 21° C., and stirred for 3 hours. The reaction mixture was washed with water (50 mL); 0.01 N HCl (50 mL) and the organic layer was concentrated in vacuo to give an oil. Heptane (150 mL) was added and the mixture was concentrated in vacuo to azeotropically remove water and dichloromethane. This azeotropic procedure was repeated two more times using heptane (150 mL) to give a final volume of about 100 mL. The resulting organic solution was charged to a 200 mL three-necked round bottom flask and cooled to 15° C. in a water bath. Pieces of ice were added slowly to the water bath to cool the mixture to 5° C. in a period of 40 minutes (the mixture was seeded at approximately 10° C.). The cloudy mixture was further cooled to −10° C. and stirred for 2.5 hours. The resulting suspension was filtered through a Buchner funnel and the precipitate was washed with ice cold heptane (20 mL×2). The precipitate was collected and dried in vacuo (25 mmHg) for 6 hours to give N-FMOC-2-(n-decylamino)acetaldehyde (25.6 g; 61% yield; 99% purity) as a white waxy powder. A three-necked, 1000 mL round bottom flask equipped with a magnetic stir bar and a gas inlet tubing purged with a stream of dilute ozone in oxygen for 2.5 hours (internal temperature about −55° C.; flow rate for dilute ozone in oxygen about 1.0 L/min) was monitored by HPLC (retention time for starting material=7.96 min; retention time for product=5.82 min) the mixture was purged with nitrogen for 20 minutes to remove excess ozone warmed to 21° C. The reaction mixture was washed with water (50 mL) 0.01 N HCl (50 mL) and the organic layer was concentrated in vacuo to give an oil the mixture was concentrated in vacuo to azeotropically remove water and dichloromethane to give a final volume of about 100 mL The resulting organic solution was charged to a 200 mL three-necked round bottom flask cooled to 15° C. in a water bath to cool the mixture to 5° C. in a period of 40 minutes (the mixture was seeded at approximately 10° C. The cloudy mixture was further cooled to −10° C. stirred for 2.5 hours The resulting suspension was filtered through a Buchner funnel the precipitate was washed with ice cold heptane (20 mL×2) The precipitate was collected dried in vacuo (25 mmHg) for 6 hours

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of oxalyl chloride (12.24 ml) and methylene chloride (50 mL) at −35 to −45° C. was added DMSO (14.75 g) in methylene chloride (25 mL) over 20 minutes. The reaction mixture was stirred for 10 minutes at −35 to −45° C. A solution of N-Fmoc-decylaminoethanol (20.0 g) in methylene chloride (70 mL) was added over 25 minutes and then stirred 40 minutes at −35 to −45° C. Triethylamine (21.49 g) was then added and the mixture stirred for 30 minutes at −10 to −20° C. The reaction mixture was quenched with water (120 mL) followed by concentrated sulfuric acid (20.0 g) while maintaining the internal temperature at 0-5° C. The organic layer was isolated and washed with 2% sulfuric acid (100 mL) followed by water (2×100 mL). The organic solution was distilled under vacuum at 60° C. to about 100 mL. Heptane (100 mL) was added, the temperature of the oil bath raised to 80° C. and the distillation was continued until the residual volume was 100 mL. More heptane (100 mL) was added and the distillation repeated to a volume of 100 mL. The heating bath was replaced with a cold water bath at 15° C. The bath was cooled slowly to 5° C. over 20 minutes to start the precipitation of the product. The slurry was then cooled to −5 to −10° C. and the slurry was stirred for 2 hours. The solid was then collected on a Buchner funnel and washed with cold (−5° C.) heptane (2×15 mL). The wet solid was dried in vacuo to yield the aldehyde. stirred 40 minutes at −35 to −45° C the mixture stirred for 30 minutes at −10 to −20° C The reaction mixture was quenched with water (120 mL) while maintaining the internal temperature at 0-5° C The organic layer was isolated washed with 2% sulfuric acid (100 mL) The organic solution was distilled under vacuum at 60° C. to about 100 mL Heptane (100 mL) was added the temperature of the oil bath raised to 80° C. the distillation More heptane (100 mL) was added the distillation The heating bath was replaced with a cold water bath at 15° C The bath was cooled slowly to 5° C. over 20 minutes the precipitation of the product The slurry was then cooled to −5 to −10° C. the slurry was stirred for 2 hours The solid was then collected on a Buchner funnel washed with cold (−5° C.) heptane (2×15 mL) The wet solid was dried in vacuo

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of oxalyl chloride (12.24 mL) and methylene chloride (50 mL) at −35 to −45° C. was added DMSO (14.75 g) in methylene chloride (25 mL) over 20 minutes. The reaction mixture was stirred for 10 minutes at −35 to −45° C. A solution of N-Fmoc-2-(n-decylamino)ethanol (20.0 g) in methylene chloride (70 mL) was added over 25 minutes and then stirred 40 minutes at −35 to −45° C. Triethylamine (21.49 g) was then added and the mixture stirred for 30 minutes at −10 to −20° C. The reaction mixture was quenched with water (120 mL) followed by concentrated sulfuric acid (20.0 g) while maintaining the internal temperature at 0-5° C. The organic layer was isolated and washed with 2% sulfuric acid (100 mL) followed by water (2×100 mL). The organic solution was distilled under vacuum at 60° C. to about 100 mL. Heptane (100 mL) was added, the temperature of the oil bath raised to 80° C. and the distillation was continued until the residual volume was 100 mL. More heptane (100 mL) was added and the distillation repeated to a volume of 100 mL. The heating bath was replaced with a cold water bath at 15° C. The bath was cooled slowly to 5° C. over 20 minutes to start the precipitation of the product. The slurry was then cooled to −5 to −10° C. and the slurry was stirred for 2 hours. The solid was then collected on a Buchner funnel and washed with cold (−5° C.) heptane (2×15 mL). The wet solid was dried in vacuo to yield the title aldehyde. stirred 40 minutes at −35 to −45° C the mixture stirred for 30 minutes at −10 to −20° C The reaction mixture was quenched with water (120 mL) while maintaining the internal temperature at 0-5° C The organic layer was isolated washed with 2% sulfuric acid (100 mL) The organic solution was distilled under vacuum at 60° C. to about 100 mL Heptane (100 mL) was added the temperature of the oil bath raised to 80° C. the distillation More heptane (100 mL) was added the distillation The heating bath was replaced with a cold water bath at 15° C The bath was cooled slowly to 5° C. over 20 minutes the precipitation of the product The slurry was then cooled to −5 to −10° C. the slurry was stirred for 2 hours The solid was then collected on a Buchner funnel washed with cold (−5° C.) heptane (2×15 mL) The wet solid was dried in vacuo

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of oxalyl chloride (12.24 mL) and methylene chloride (50 mL) at −35 to −45° C. was added DMSO (14.75 g) in methylene chloride (25 mL) over 20 minutes. The reaction mixture was stirred for 10 minutes at −35 to −45° C. A solution of N-Fmoc-2-(n-decylamino)ethanol (20.0 g) in methylene chloride (70 mL) was added over 25 minutes and then stirred 40 minutes at −35 to −45° C. Triethylamine (21.49 g) was then added and the mixture stirred for 30 minutes at −10 to −20° C. The reaction mixture was quenched with water (120 mL) followed by concentrated sulfuric acid (20.0 g) while maintaining the internal temperature at 0-5° C. The organic layer was isolated and washed with 2% sulfuric acid (100 mL) followed by water (2×100 mL). The organic solution was distilled under vacuum at 60° C. to about 100 mL. Heptane (100 mL) was added, the temperature of the oil bath raised to 80° C. and the distillation was continued until the residual volume was 100 mL. More heptane (100 mL) was added and the distillation repeated to a volume of 100 mL. The heating bath was replaced with a cold water bath at 15° C. The bath was cooled slowly to 5° C. over 20 minutes to start the precipitation of the product. The slurry was then cooled to −5 to −10° C. and the slurry was stirred for 2 hours. The solid was then collected on a Buchner funnel and washed with cold (−5° C.) heptane (2×15 mL). The wet solid was dried in vacuo to yield the title aldehyde. stirred 40 minutes at −35 to −45° C the mixture stirred for 30 minutes at −10 to −20° C The reaction mixture was quenched with water (120 mL) while maintaining the internal temperature at 0-5° C The organic layer was isolated washed with 2% sulfuric acid (100 mL) The organic solution was distilled under vacuum at 60° C. to about 100 mL Heptane (100 mL) was added the temperature of the oil bath raised to 80° C. the distillation More heptane (100 mL) was added the distillation The heating bath was replaced with a cold water bath at 15° C The bath was cooled slowly to 5° C. over 20 minutes the precipitation of the product The slurry was then cooled to −5 to −10° C. the slurry was stirred for 2 hours The solid was then collected on a Buchner funnel washed with cold (−5° C.) heptane (2×15 mL) The wet solid was dried in vacuo

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of oxalyl chloride (12.24 mL) and methylene chloride (50 mL) at −35 to −45° C. was added DMSO (14.75 g) in methylene chloride (25 mL) over 20 minutes. The reaction mixture was stirred for 10 minutes at −35 to −45° C. A solution of N-Fmoc-2-(n-decylamino)ethanol (20.0 g) in methylene chloride (70 mL) was added over 25 minutes and then stirred 40 minutes at −35 to −45° C. Triethylamine (21.49 g) was then added and the mixture stirred for 30 minutes at −10 to −20° C. The reaction mixture was quenched with water (120 mL) followed by concentrated sulfuric acid (20.0 g) while maintaining the internal temperature at 0-5° C. The organic layer was isolated and washed with 2% sulfuric acid (100 mL) followed by water (2×100 mL). The organic solution was distilled under vacuum at 60° C. to about 100 mL. Heptane (100 mL) was added, the temperature of the oil bath raised to 80° C. and the distillation was continued until the residual volume was 100 mL. More heptane (100 mL) was added and the distillation repeated to a volume of 100 mL. The heating bath was replaced with a cold water bath at 15° C. The bath was cooled slowly to 5° C. over 20 minutes to start the precipitation of the product. The slurry was then cooled to −5 to −10° C. and the slurry was stirred for 2 hours. The solid was then collected on a Buchner funnel and washed with cold (−5° C.) heptane (2×15 mL). The wet solid was dried in vacuo to yield the title aldehyde. stirred 40 minutes at −35 to −45° C the mixture stirred for 30 minutes at −10 to −20° C The reaction mixture was quenched with water (120 mL) while maintaining the internal temperature at 0-5° C The organic layer was isolated washed with 2% sulfuric acid (100 mL) The organic solution was distilled under vacuum at 60° C. to about 100 mL Heptane (100 mL) was added the temperature of the oil bath raised to 80° C. the distillation More heptane (100 mL) was added the distillation The heating bath was replaced with a cold water bath at 15° C The bath was cooled slowly to 5° C. over 20 minutes the precipitation of the product The slurry was then cooled to −5 to −10° C. the slurry was stirred for 2 hours The solid was then collected on a Buchner funnel washed with cold (−5° C.) heptane (2×15 mL) The wet solid was dried in vacuo

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of oxalyl chloride (12.24 mL) and methylene chloride (50 mL) at −35 to −45° C. was added DMSO (14.75 g) in methylene chloride (25 mL) over 20 minutes. The reaction mixture was stirred for 10 minutes at −35 to −45° C. A solution of N-Fmoc-2-(n-decylamino)ethanol (20.0 g) in methylene chloride (70 mL) was added over 25 minutes and then stirred 40 minutes at −35 to −45° C. Triethylamine (21.49 g) was then added and the mixture stirred for 30 minutes at −10 to −20° C. The reaction mixture was quenched with water (120 mL) followed by concentrated sulfuric acid (20.0 g) while maintaining the internal temperature at 0-5° C. The organic layer was isolated and washed with 2% sulfuric acid (100 mL) followed by water (2×100 mL). The organic solution was distilled under vacuum at 60° C. to about 100 mL. Heptane (100 mL) was added, the temperature of the oil bath raised to 80° C. and the distillation was continued until the residual volume was 100 mL. More heptane (100 mL) was added and the distillation repeated to a volume of 100 mL. The heating bath was replaced with a cold water bath at 15° C. The bath was cooled slowly to 5° C. over 20 minutes to start the precipitation of the product. The slurry was then cooled to −5 to −10° C. and the slurry was stirred for 2 hours. The solid was then collected on a Buchner funnel and washed with cold (−5° C.) heptane (2×15 mL). The wet solid was dried in vacuo to yield the title aldehyde. stirred 40 minutes at −35 to −45° C the mixture stirred for 30 minutes at −10 to −20° C The reaction mixture was quenched with water (120 mL) while maintaining the internal temperature at 0-5° C The organic layer was isolated washed with 2% sulfuric acid (100 mL) The organic solution was distilled under vacuum at 60° C. to about 100 mL Heptane (100 mL) was added the temperature of the oil bath raised to 80° C. the distillation More heptane (100 mL) was added the distillation The heating bath was replaced with a cold water bath at 15° C The bath was cooled slowly to 5° C. over 20 minutes the precipitation of the product The slurry was then cooled to −5 to −10° C. the slurry was stirred for 2 hours The solid was then collected on a Buchner funnel washed with cold (−5° C.) heptane (2×15 mL) The wet solid was dried in vacuo

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of oxalyl chloride (12.24 ml) and methylene chloride (50 mL) at −35 to −45° C. was added DMSO (14.75 g) in methylene chloride (25 mL) over 20 minutes. The reaction mixture was stirred for 10 minutes at −35 to −45° C. A solution of N-Fmoc-decylaminoethanol (20.0 g) in methylene chloride (70 mL) was added over 25 minutes and then stirred 40 minutes at −35 to −45° C. Triethylamine (21.49 g) was then added and the mixture stirred for 30 minutes at −10 to −20° C. The reaction mixture was quenched with water (120 mL) followed by concentrated sulfuric acid (20.0 g) while maintaining the internal temperature at 0-5° C. The organic layer was isolated and washed with 2% sulfuric acid (100 mL) followed by water (2×100 mL). The organic solution was distilled under vacuum at 60° C. to about 100 mL. Heptane (100 mL) was added, the temperature of the oil bath raised to 80° C. and the distillation was continued until the residual volume was 100 mL. More heptane (100 mL) was added and the distillation repeated to a volume of 100 mL. The heating bath was replaced with a cold water bath at 15° C. The bath was cooled slowly to 5° C. over 20 minutes to start the precipitation of the product. The slurry was then cooled to −5 to −10° C. and the slurry was stirred for 2 hours. The solid was then collected on a Buchner funnel and washed with cold (−5° C.) heptane (2×15 mL). The wet solid was dried in vacuo to yield the aldehyde. stirred 40 minutes at −35 to −45° C the mixture stirred for 30 minutes at −10 to −20° C The reaction mixture was quenched with water (120 mL) while maintaining the internal temperature at 0-5° C The organic layer was isolated washed with 2% sulfuric acid (100 mL) The organic solution was distilled under vacuum at 60° C. to about 100 mL Heptane (100 mL) was added the temperature of the oil bath raised to 80° C. the distillation More heptane (100 mL) was added the distillation The heating bath was replaced with a cold water bath at 15° C The bath was cooled slowly to 5° C. over 20 minutes the precipitation of the product The slurry was then cooled to −5 to −10° C. the slurry was stirred for 2 hours The solid was then collected on a Buchner funnel washed with cold (−5° C.) heptane (2×15 mL) The wet solid was dried in vacuo

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of oxalyl chloride (12.24 mL) and methylene chloride (50 mL) at −35 to −45° C. was added DMSO (14.75 g) in methylene chloride (25 mL) over 20 minutes. The reaction mixture was stirred for 10 minutes at −35 to −45° C. A solution of N-Fmoc-2-(n-decylamino)ethanol (20.0 g) in methylene chloride (70 mL) was added over 25 minutes and then stirred 40 minutes at −35 to −45° C. Triethylamine (21.49 g) was then added and the mixture stirred for 30 minutes at −10 to −20° C. The reaction mixture was quenched with water (120 mL) followed by concentrated sulfuric acid (20.0 g) while maintaining the internal temperature at 0-5° C. The organic layer was isolated and washed with 2% sulfuric acid (100 mL) followed by water (2×100 mL). The organic solution was distilled under vacuum at 60° C. to about 100 mL. Heptane (100 mL) was added, the temperature of the oil bath raised to 80° C. and the distillation was continued until the residual volume was 100 mL. More heptane (100 mL) was added and the distillation repeated to a volume of 100 mL. The heating bath was replaced with a cold water bath at 15° C. The bath was cooled slowly to 5° C. over 20 minutes to start the precipitation of the product. The slurry was then cooled to −5 to −10° C. and the slurry was stirred for 2 hours. The solid was then collected on a Buchner funnel and washed with cold (−5° C.) heptane (2×15 mL). The wet solid was dried in vacuo to yield the title aldehyde. stirred 40 minutes at −35 to −45° C the mixture stirred for 30 minutes at −10 to −20° C The reaction mixture was quenched with water (120 mL) while maintaining the internal temperature at 0-5° C The organic layer was isolated washed with 2% sulfuric acid (100 mL) The organic solution was distilled under vacuum at 60° C. to about 100 mL Heptane (100 mL) was added the temperature of the oil bath raised to 80° C. the distillation More heptane (100 mL) was added the distillation The heating bath was replaced with a cold water bath at 15° C The bath was cooled slowly to 5° C. over 20 minutes the precipitation of the product The slurry was then cooled to −5 to −10° C. the slurry was stirred for 2 hours The solid was then collected on a Buchner funnel washed with cold (−5° C.) heptane (2×15 mL) The wet solid was dried in vacuo

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of oxalyl chloride (12.24 ml) and methylene chloride (50 mL) at −35 to −45° C. was added DMSO (14.75 g) in methylene chloride (25 mL) over 20 minutes. The reaction mixture was stirred for 10 minutes at −35 to −45° C. A solution of N-Fmoc-decylaminoethanol (20.0 g) in methylene chloride (70 mL) was added over 25 minutes and then stirred 40 minutes at −35 to −45° C. Triethylamine (21.49 g) was then added and the mixture stirred for 30 minutes at −10 to −20° C. The reaction mixture was quenched with water (120 mL) followed by concentrated sulfuric acid (20.0 g) while maintaining the internal temperature at 0-5° C. The organic layer was isolated and washed with 2% sulfuric acid (100 mL) followed by water (2×100 mL). The organic solution was distilled under vacuum at 60° C. to about 100 mL. Heptane (100 mL) was added, the temperature of the oil bath raised to 80° C. and the distillation was continued until the residual volume was 100 mL. More heptane (100 mL) was added and the distillation repeated to a volume of 100 mL. The heating bath was replaced with a cold water bath at 15° C. The bath was cooled slowly to 5° C. over 20 minutes to start the precipitation of the product. The slurry was then cooled to −5 to −10° C. and the slurry was stirred for 2 hours. The solid was then collected on a Buchner funnel and washed with cold (−5° C.) heptane (2×15 mL). The wet solid was dried in vacuo to yield the aldehyde. stirred 40 minutes at −35 to −45° C the mixture stirred for 30 minutes at −10 to −20° C The reaction mixture was quenched with water (120 mL) while maintaining the internal temperature at 0-5° C The organic layer was isolated washed with 2% sulfuric acid (100 mL) The organic solution was distilled under vacuum at 60° C. to about 100 mL Heptane (100 mL) was added the temperature of the oil bath raised to 80° C. the distillation More heptane (100 mL) was added the distillation The heating bath was replaced with a cold water bath at 15° C The bath was cooled slowly to 5° C. over 20 minutes the precipitation of the product The slurry was then cooled to −5 to −10° C. the slurry was stirred for 2 hours The solid was then collected on a Buchner funnel washed with cold (−5° C.) heptane (2×15 mL) The wet solid was dried in vacuo