6-oxoheptanoic acid

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a rapidly stirred mixture of diethyl ether (175 ml) and 40% KOH (52 ml) at 0° C. was added MNNG (15.4 g, 105 mmol). The mixture was stirred for 10 minutes. The ethereal layer was transferred to a solution of 6-oxo-heptanoic acid 1-1 (5.0 g, 34.68 mmol) and CH2Cl2 at 0° C. The solution was purged with argon for 30 minutes and then concentrated. Flash chromatography (silica, 30% to 50% EtOAc/hexanes) gave ester 1-2 as a clear oil. The solution was purged with argon for 30 minutes concentrated

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

Procedure: The mixed anhydride coupling was performed as described for the synthesis of compound 13 with 6-oxo-n-heptanoic acid (97 mg, 0.67 mmol) and the product from above, compound 15 (238 mg, 0.67 mmol). Each component was dissolved in 10 ml of dry tetrahydrofaran. Yield 111 mg (34%), mp 177.5°-180.5° C., [α]D25 =+19.5 (c.=1.4, methanol). Anal. calc. for C27H33N3O6 (493.58): C, 65.44; H, 6.71; N, 8.48. Found: C, 65.46; H, 6.74; N, 8.61. Each component was dissolved in 10 ml of dry tetrahydrofaran

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

Procedure: The mixed anhydride coupling was performed as described for the synthesis of compound 13 with 6-oxo-n-heptanoic acid (97 mg, 0.67 mmol) and the product from above, compound 15 (238 mg, 0.67 mmol). Each component was dissolved in 10 ml of dry tetrahydrofaran. Yield 111 mg (34%), mp 177.5°-180.5° C., [α]D25 =+19.5 (c.=1.4, methanol). Anal. calc. for C27H33N3O6 (493.58): C, 65.44; H, 6.71; N, 8.48. Found: C, 65.46; H, 6.74; N, 8.61. Each component was dissolved in 10 ml of dry tetrahydrofaran

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

Procedure: 10.0 g (about 90% pure, 62.4 mmol) of 6-oxoheptanoic acid were initially charged in 71.8 ml of cyclohexane, and 20.46 g (93.6 mmol) of tert-butyl 2,2,2-trichloroacetimidate and 15 ml of dichloromethane were added. At −10° C. 0.55 ml (6.24 mmol) of trifluoromethanesulfonic acid were slowly added dropwise to the solution. The resulting suspension was stirred overnight with warming to RT. The insoluble precipitate was then removed by filtration. The filtrate was washed twice with sodium bicarbonate solution and with saturated sodium chloride solution, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 5:1). On standing overnight, a solid precipitated from the product obtained in this manner. This solid was removed by filtration with suction and discarded. The target product, obtained in the form of the filtrate, was not purified any further. This gave 4.51 g (36.1% of theory) of the title compound. At −10° C The insoluble precipitate was then removed by filtration The filtrate was washed twice with sodium bicarbonate solution and with saturated sodium chloride solution dried over magnesium sulfate concentrated under reduced pressure The residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 5:1) On standing overnight a solid precipitated from the product obtained in this manner This solid was removed by filtration with suction The target product, obtained in the form of the filtrate was not purified any further

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 6-oxo-heptanoic acid 7-1(100 g, 694 mmol), NEt3 (111.3 ml, 763.4 mmol) and THF (2000 mL) at -78° C. was added pivaloyl chloride (98.7 ml, 763.4 mmol). The mixture was warmed to 0° C. for 1.0 h and then recooled to -78° C. To a stirred solution of (S)-(-)-4-benzyl-2-oxazolidinone (136 g, 763.4 mmol) and THF (2000 ml) at -78° C. was added nBuLi (306 ml, 765 mmol, 2.5M in hexanes) dropwise over 30 minutes. After 20 minutes, the lithium reagent was transferred to the mixed anhydride via cannula. After 20 minutes, the reaction was warmed to 0° C. for 1.0 h. The mixture was diluted with ethyl acetate, washed with sat. NaHCO3, brine, and dried over MgSO4. Following evaporative removal of the solvent, the residue was azeotroped with xylenes to give 7-2 as a colorless foam. recooled to -78° C After 20 minutes the reaction was warmed to 0° C. for 1.0 h washed with sat. NaHCO3, brine dried over MgSO4 removal of the solvent the residue was azeotroped with xylenes

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

Procedure: To a rapidly stirred mixture of diethyl ether (175 ml) and 40% KOH (52 ml) at 0° C. was added MNNG (15.4 g, 105 mmol). The mixture was stirred for 10 minutes. The ethereal layer was transferred to a solution of 6-oxo-heptanoic acid 1-1 (5.0 g, 34.68 mmol) and CH2Cl2 at 0° C. The solution was purged with argon for 30 minutes and then concentrated. Flash chromatography (silica, 30% to 50% EtOAc/hexanes) gave ester 1-2 as a clear oil. The solution was purged with argon for 30 minutes concentrated

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

Procedure: To a rapidly stirred mixture of diethyl ether (175 ml) and 40% KOH (52 ml) at 0° C. was added MNNG (15.4 g, 105 mmol). The mixture was stirred for 10 minutes. The ethereal layer was transferred to a solution of 6-oxo-heptanoic acid 1-1 (5.0 g, 34.68 mmol) and CH2Cl2 at 0° C. The solution was purged with argon for 30 minutes and then concentrated. Flash chromatography (silica, 30% to 50% EtOAc/hexanes) gave ester 1-2 as a clear oil. The solution was purged with argon for 30 minutes concentrated

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

Procedure: 1,8-Diazabicyclo[5.4.0]undec-7-ene (3.4 mL, 22.86 mmol) was added to a solution of 6-oxoheptanoic acid 23 (1.1 g, 7.63 mmol) in acetone (15 mL) at 23° C. After stirring for 15 min iodomethane (2.4 mL, 38.3 mmol) was added. The reaction was stirred for 1 h and then the solvent was removed in vacuo. The residue was purified by flash column chromatography (silica gel, 7:3 hex/EtOAc) to provide 1.18 g (95%) of the methyl ester 24 (see scheme 4). was added the solvent was removed in vacuo The residue was purified by flash column chromatography (silica gel, 7:3 hex/EtOAc)

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

Procedure: To a rapidly stirred mixture of diethyl ether (175 ml) and 40% KOH (52 ml) at 0° C. was added MNNG (15.4 g, 105 mmol). The mixture was stirred for 10 minutes. The ethereal layer was transferred to a solution of 6-oxo-heptanoic acid 1-1 (5.0 g, 34.68 mmol) and CH2Cl2 at 0° C. The solution was purged with argon for 30 minutes and then concentrated. Flash chromatography (silica, 30% to 50% EtOAc/hexanes) gave ester 1-2 as a clear oil. The solution was purged with argon for 30 minutes concentrated

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

Procedure: To a rapidly stirred mixture of diethyl ether (175 ml) and 40% KOH (52 ml) at 0° C. was added MNNG (15.4 g, 105 mmol). The mixture was stirred for 10 minutes. The ethereal layer was transferred to a solution of 6-oxo-heptanoic acid 1-1 (5.0 g, 34.68 mmol) and CH2Cl2 at 0° C. The solution was purged with argon for 30 minutes and then concentrated. Flash chromatography (silica, 30% to 50% EtOAc/hexanes) gave ester 1-2 as a clear oil. The solution was purged with argon for 30 minutes concentrated