5-[tert-butyl(dimethyl)silyl]oxypentanal

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: A solution of 4-[3-bromomethyl-2-((E)-2-ethoxycarbonyl-vinyl)-phenoxy]-butyric acid ethyl ester (2.0 mmol, 798 mg) and triphenylphosphine (2.2 mmol, 577 mg) in acetonitrile (12 mL) was heated to reflux for 1 h under nitrogen atmosphere. Then, it was cooled to room temperature and a solution of 5-(tert-butyl-dimethyl-silanyloxy)-pentanal (2.8 mmol, 606 mg) in 1,2-epoxybutane (22 mL) was added at room temperature and the mixture was again heated to reflux for 15 h. During this period, the mixture first turned to a brick red color and at the end of the reaction it had become a pale yellow solution. Then, the reaction mixture was cooled to room temperature and the solvent was removed under vacuum. The residue was dissolved in a solution of ethyl acetate and hexanes (1:3, 150 mL) and the resulting cloudy solution was washed with a mixture of methanol and water (2:1, 225 mL). The aqueous layer was extracted one more time with ethyl acetate and hexanes (1:3, 50 mL). The combined organic extracts were washed with brine solution (150 mL) and the organic solution was dried over anhydrous magnesium sulfate. Filtration of the drying agent and the removal of the solvent gave light brown oil. The crude mixture was purified by using a Biotage (40L) column chromatograph eluting with 5 and 15% ethyl acetate in hexanes to obtain the desired 4-[3-[6-(tert-butyl-dimethyl-silanyloxy)-hex-1-enyl]-2-((E)-2-ethoxycarbonyl-vinyl)-phenoxy]-butyric acid ethyl ester (760 mg, 74%) as a colorless oil: ES(+)-HRMS m/e calculated for C29H46O6Si (M+Na)+ 541.2956, found 541.2953. to reflux for 1 h under nitrogen atmosphere the mixture was again heated to reflux for 15 h During this period the mixture first turned to a brick red color and at the end of the reaction it Then, the reaction mixture was cooled to room temperature the solvent was removed under vacuum The residue was dissolved in a solution of ethyl acetate and hexanes (1:3, 150 mL) the resulting cloudy solution was washed with a mixture of methanol and water (2:1, 225 mL) The aqueous layer was extracted one more time with ethyl acetate and hexanes (1:3, 50 mL) The combined organic extracts were washed with brine solution (150 mL) the organic solution was dried over anhydrous magnesium sulfate Filtration of the drying agent the removal of the solvent gave light brown oil The crude mixture was purified eluting with 5 and 15% ethyl acetate in hexanes

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

Procedure: To a solution of 5-(tert-butyl-dimethyl-silanyloxy)-pentanol (16.8 mmol, 3.66 g) in dichloromethane (30 mL) were added water (5.6 mL), potassium bromide (1.7 mmol, 202 mg), n-tetrabutylammonium hydrogensulfate (0.84 mmol, 290 mg), and TEMPO (30 mg) at room temperature. The resulting light brown solution was cooled to ˜5° C. and a solution of sodium hypochlorite (19.3 mmol, 30 mL, 5%) was added dropwise at this temperature. After addition of half of the sodium hypochlorite solution, solid potassium carbonate (300 mg) was added to maintain the reaction mixture basic. Then, the remaining sodium hypochlorite solution was added at 5-10° C. By this point, a precipitate had formed and the reaction mixture was stirred for another 1 h at ˜10-15° C. Then, water (100 mL) was added and the resulting solution was extracted into diethyl ether (2×100 mL). The combined organic extracts were washed with brine solution (150 mL) and the organic layer was dried over anhydrous magnesium sulfate. Filtration of the drying agent and the removal of the solvent gave 5-(tert-butyl-dimethyl-silanyloxy)-pentanal (3.32 g, 91%) as a light brown oil: ES(+)-HRMS m/e calculated for C11H24O2Si (M+H)+ 217.1619, found 217.1619. was added to maintain the reaction mixture basic By this point, a precipitate had formed the resulting solution was extracted into diethyl ether (2×100 mL) The combined organic extracts were washed with brine solution (150 mL) the organic layer was dried over anhydrous magnesium sulfate Filtration of the drying agent the removal of the solvent

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

Procedure: A solution of 4-[3-bromomethyl-2-((E)-2-ethoxycarbonyl-vinyl)-phenoxy]-butyric acid ethyl ester (2.0 mmol, 798 mg) and triphenylphosphine (2.2 mmol, 577 mg) in acetonitrile (12 mL) was heated to reflux for 1 h under nitrogen atmosphere. Then, it was cooled to room temperature and a solution of 5-(tert-butyl-dimethyl-silanyloxy)-pentanal (2.8 mmol, 606 mg) in 1,2-epoxybutane (22 mL) was added at room temperature and the mixture was again heated to reflux for 15 h. During this period, the mixture first turned to a brick red color and at the end of the reaction it had become a pale yellow solution. Then, the reaction mixture was cooled to room temperature and the solvent was removed under vacuum. The residue was dissolved in a solution of ethyl acetate and hexanes (1:3, 150 mL) and the resulting cloudy solution was washed with a mixture of methanol and water (2:1, 225 mL). The aqueous layer was extracted one more time with ethyl acetate and hexanes (1:3, 50 mL). The combined organic extracts were washed with brine solution (150 mL) and the organic solution was dried over anhydrous magnesium sulfate. Filtration of the drying agent and the removal of the solvent gave light brown oil. The crude mixture was purified by using a Biotage™ (40 L) column chromatograph eluting with 5 and 15% ethyl acetate in hexanes to obtain the desired 4-[3-[6-(tert-butyl-dimethyl-silanyloxy)-hex-1-enyl]-2-((E)-2-ethoxycarbonyl-vinyl)-phenoxy]-butyric acid ethyl ester (760 mg, 74%) as a colorless oil: ES(+)-HRMS m/e calculated for C29H46O6Si (M+Na)+ 541.2956, found 541.2953. to reflux for 1 h under nitrogen atmosphere the mixture was again heated to reflux for 15 h During this period the mixture first turned to a brick red color and at the end of the reaction it Then, the reaction mixture was cooled to room temperature the solvent was removed under vacuum The residue was dissolved in a solution of ethyl acetate and hexanes (1:3, 150 mL) the resulting cloudy solution was washed with a mixture of methanol and water (2:1, 225 mL) The aqueous layer was extracted one more time with ethyl acetate and hexanes (1:3, 50 mL) The combined organic extracts were washed with brine solution (150 mL) the organic solution was dried over anhydrous magnesium sulfate Filtration of the drying agent the removal of the solvent gave light brown oil The crude mixture was purified eluting with 5 and 15% ethyl acetate in hexanes

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

Procedure: To a solution of 5-(tert-butyl-dimethyl-silanyloxy)-pentanol (16.8 mmol, 3.66 g) in dichloromethane (30 mL) were added water (5.6 mL), potassium bromide (1.7 mmol, 202 mg), n-tetrabutylammonium hydrogensulfate (0.84 mmol, 290 mg), and TEMPO (30 mg) at room temperature. The resulting light brown solution was cooled to ˜5° C. and a solution of sodium hypochlorite (19.3 mmol, 30 mL, 5%) was added dropwise at this temperature. After addition of half of the sodium hypochlorite solution, solid potassium carbonate (300 mg) was added to maintain the reaction mixture basic. Then, the remaining sodium hypochlorite solution was added at 5-10° C. By this point, a precipitate had formed and the reaction mixture was stirred for another 1 h at ˜10-15° C. Then, water (100 mL) was added and the resulting solution was extracted into diethyl ether (2×100 mL). The combined organic extracts were washed with brine solution (150 mL) and the organic layer was dried over anhydrous magnesium sulfate. Filtration of the drying agent and the removal of the solvent gave 5-(tert-butyl-dimethyl-silanyloxy)-pentanal (3.32 g, 91%) as a light brown oil: ES(+)-HRMS m/e calculated for C11H24O2Si (M+H)+ 217.1619, found 217.1619. was added to maintain the reaction mixture basic By this point, a precipitate had formed the resulting solution was extracted into diethyl ether (2×100 mL) The combined organic extracts were washed with brine solution (150 mL) the organic layer was dried over anhydrous magnesium sulfate Filtration of the drying agent the removal of the solvent

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

Procedure: A solution of 4-[3-bromomethyl-2-((E)-2-ethoxycarbonyl-vinyl)-phenoxy]-butyric acid ethyl ester (2.0 mmol, 798 mg) and triphenylphosphine (2.2 mmol, 577 mg) in acetonitrile (12 mL) was heated to reflux for 1 h under nitrogen atmosphere. Then, it was cooled to room temperature and a solution of 5-(tert-butyl-dimethyl-silanyloxy)-pentanal (2.8 mmol, 606 mg) in 1,2-epoxybutane (22 mL) was added at room temperature and the mixture was again heated to reflux for 15 h. During this period, the mixture first turned to a brick red color and at the end of the reaction it had become a pale yellow solution. Then, the reaction mixture was cooled to room temperature and the solvent was removed under vacuum. The residue was dissolved in a solution of ethyl acetate and hexanes (1:3, 150 mL) and the resulting cloudy solution was washed with a mixture of methanol and water (2:1, 225 mL). The aqueous layer was extracted one more time with ethyl acetate and hexanes (1:3, 50 mL). The combined organic extracts were washed with brine solution (150 mL) and the organic solution was dried over anhydrous magnesium sulfate. Filtration of the drying agent and the removal of the solvent gave light brown oil. The crude mixture was purified by using a Biotage™ (40 L) column chromatograph eluting with 5 and 15% ethyl acetate in hexanes to obtain the desired 4-[3-[6-(tert-butyl-dimethyl-silanyloxy)-hex-1-enyl]-2-((E)-2-ethoxycarbonyl-vinyl)-phenoxy]-butyric acid ethyl ester (760 mg, 74%) as a colorless oil: ES(+)-HRMS m/e calculated for C29H46O6Si (M+Na)+ 541.2956. found 541.2953. to reflux for 1 h under nitrogen atmosphere the mixture was again heated to reflux for 15 h During this period the mixture first turned to a brick red color and at the end of the reaction it Then, the reaction mixture was cooled to room temperature the solvent was removed under vacuum The residue was dissolved in a solution of ethyl acetate and hexanes (1:3, 150 mL) the resulting cloudy solution was washed with a mixture of methanol and water (2:1, 225 mL) The aqueous layer was extracted one more time with ethyl acetate and hexanes (1:3, 50 mL) The combined organic extracts were washed with brine solution (150 mL) the organic solution was dried over anhydrous magnesium sulfate Filtration of the drying agent the removal of the solvent gave light brown oil The crude mixture was purified eluting with 5 and 15% ethyl acetate in hexanes

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

Procedure: To a solution of 5-(tert-butyl-dimethyl-silanyloxy)-pentanol (16.8 mmol, 3.66 g) in dichloromethane (30 mL) were added water (5.6 mL), potassium bromide (1.7 mmol, 202 mg), n-tetrabutylammonium hydrogensulfate (0.84 mmol, 290 mg), and TEMPO (30 mg) at room temperature. The resulting light brown solution was cooled to ˜5° C. and a solution of sodium hypochlorite (19.3 mmol, 30 mL, 5%) was added dropwise at this temperature. After addition of half of the sodium hypochlorite solution, solid potassium carbonate (300 mg) was added to maintain the reaction mixture basic. Then, the remaining sodium hypochlorite solution was added at 5-10° C. By this point, a precipitate had formed and the reaction mixture was stirred for another 1 h at ˜10-15° C. Then, water (100 mL) was added and the resulting solution was extracted into diethyl ether (2×100 mL). The combined organic extracts were washed with brine solution (150 mL) and the organic layer was dried over anhydrous magnesium sulfate. Filtration of the drying agent and the removal of the solvent gave 5-(tert-butyl-dimethyl-silanyloxy)-pentanal (3.32 g, 91%) as a light brown oil: ES(+)-HRMS m/e calculated for C11H24O2Si (M+H)+ 217.1619. found 217.1619. was added to maintain the reaction mixture basic By this point, a precipitate had formed the resulting solution was extracted into diethyl ether (2×100 mL) The combined organic extracts were washed with brine solution (150 mL) the organic layer was dried over anhydrous magnesium sulfate Filtration of the drying agent the removal of the solvent

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

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

Procedure: Under a nitrogen atmosphere and at 0° C., dimethylsulfoxide (7.81 ml, 110 mmol), triethylamine (9.60 ml, 69.0 mmol), and a sulfur trioxide-pyridine complex (4.39 g, 27.6 mmol) were added to a dichloromethane solution (80 ml) of 5-(t-butyldimethylsilyloxy)pentanol (3.00 g, 13.8 mmol). The resulting mixture was stirred at 0° C. for 30 minutes and then, at room temperature for further 3 hours. After cooling to 0° C., a saturated aquoeus ammonium chloride solution was added. Dichloromethane was distilled off under reduced pressure. To the residue was added ethyl acetate. After the water layer was separated, the organic layer was washed with water and brine, dried over magnesium sulfate and then, concentrated. The residue thus obtained was subjected to chromatography on a silica gel column, and the fraction obtained from the hexane:ethyl acetate=20:1 eluate was concentrated, whereby the title compound (2.42 g, 11.2 mmol, 81%) was obtained as a colorless oil. at room temperature for further 3 hours After cooling to 0° C. Dichloromethane was distilled off under reduced pressure To the residue was added ethyl acetate After the water layer was separated the organic layer was washed with water and brine dried over magnesium sulfate concentrated The residue thus obtained ethyl acetate=20:1 eluate was concentrated

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

Procedure: A solution of 4-[3-bromomethyl-2-((E)-2-ethoxycarbonyl-vinyl)-phenoxy]-butyric acid ethyl ester (2.0 mmol, 798 mg) and triphenylphosphine (2.2 mmol, 577 mg) in acetonitrile (12 mL) was heated to reflux for 1 h under nitrogen atmosphere. Then, it was cooled to room temperature and a solution of 5-(tert-butyl-dimethyl-silanyloxy)-pentanal (2.8 mmol, 606 mg) in 1,2-epoxybutane (22 mL) was added at room temperature and the mixture was again heated to reflux for 15 h. During this period, the mixture first turned to a brick red color and at the end of the reaction it had become a pale yellow solution. Then, the reaction mixture was cooled to room temperature and the solvent was removed under vacuum. The residue was dissolved in a solution of ethyl acetate and hexanes (1:3, 150 mL) and the resulting cloudy solution was washed with a mixture of methanol and water (2:1, 225 mL). The aqueous layer was extracted one more time with ethyl acetate and hexanes (1:3, 50 mL). The combined organic extracts were washed with brine solution (150 mL) and the organic solution was dried over anhydrous magnesium sulfate. Filtration of the drying agent and the removal of the solvent gave light brown oil. The crude mixture was purified by using a Biotage (40L) column chromatograph eluting with 5 and 15% ethyl acetate in hexanes to obtain the desired 4-[3-[6-(tert-butyl-dimethyl-silanyloxy)-hex-1-enyl]-2-((E)-2-ethoxycarbonyl-vinyl)-phenoxy]-butyric acid ethyl ester (760 mg, 74%) as a colorless oil: ES(+)-HRMS m/e calculated for C29H46O6Si (M+Na)+ 541.2956, found 541.2953. to reflux for 1 h under nitrogen atmosphere the mixture was again heated to reflux for 15 h During this period the mixture first turned to a brick red color and at the end of the reaction it Then, the reaction mixture was cooled to room temperature the solvent was removed under vacuum The residue was dissolved in a solution of ethyl acetate and hexanes (1:3, 150 mL) the resulting cloudy solution was washed with a mixture of methanol and water (2:1, 225 mL) The aqueous layer was extracted one more time with ethyl acetate and hexanes (1:3, 50 mL) The combined organic extracts were washed with brine solution (150 mL) the organic solution was dried over anhydrous magnesium sulfate Filtration of the drying agent the removal of the solvent gave light brown oil The crude mixture was purified eluting with 5 and 15% ethyl acetate in hexanes

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

Procedure: To a solution of 5-(tert-butyl-dimethyl-silanyloxy)-pentanol (16.8 mmol, 3.66 g) in dichloromethane (30 mL) were added water (5.6 mL), potassium bromide (1.7 mmol, 202 mg), n-tetrabutylammonium hydrogensulfate (0.84 mmol, 290 mg), and TEMPO (30 mg) at room temperature. The resulting light brown solution was cooled to ˜5° C. and a solution of sodium hypochlorite (19.3 mmol, 30 mL, 5%) was added dropwise at this temperature. After addition of half of the sodium hypochlorite solution, solid potassium carbonate (300 mg) was added to maintain the reaction mixture basic. Then, the remaining sodium hypochlorite solution was added at 5-10° C. By this point, a precipitate had formed and the reaction mixture was stirred for another 1 h at ˜10-15° C. Then, water (100 mL) was added and the resulting solution was extracted into diethyl ether (2×100 mL). The combined organic extracts were washed with brine solution (150 mL) and the organic layer was dried over anhydrous magnesium sulfate. Filtration of the drying agent and the removal of the solvent gave 5-(tert-butyl-dimethyl-silanyloxy)-pentanal (3.32 g, 91%) as a light brown oil: ES(+)-HRMS m/e calculated for C11H24O2Si (M+H)+ 217.1619, found 217.1619. was added to maintain the reaction mixture basic By this point, a precipitate had formed the resulting solution was extracted into diethyl ether (2×100 mL) The combined organic extracts were washed with brine solution (150 mL) the organic layer was dried over anhydrous magnesium sulfate Filtration of the drying agent the removal of the solvent