methyl 8-oxooctanoate

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

Procedure: o-Tolylacetic acid (4.56 g.) in THF (50 ml.) was treated at 5°-10° C. under argon with a 1.6M solution (36.0 ml.) of butyllithium in hexane. After 1 hour the solution obtained was added dropwise to a solution of methyl 7-formylheptanoate (5.68 g.) in dry THF (50 ml.) at -30 ° to -50° C. during 30 minutes. The mixture was stirred for 1.5 hours at the same temperature. Acetic acid (3.5 ml. ) was then added carefully and the mixture was evaporated. The residue was partitioned between ether (100 ml.) and saturated sodium bicarbonate solution (50 ml.). The aqueous layer was acidified to pH 4 (HCl) and extracted thoroughly with ether. The combined extracts were washed with water, dried (MgSO4) and evaporated. The residual oil was purified by medium pressure liquid chromatography on silica (190 g.), eluting with 30% v/v ethyl acetate/hexane, to give methyl 9-carboxy-8-hydroxy-9-o-tolylnonanoate (A) as an oil (1.94 g., single diastereoisomer);NMR : 1-1.7 (10H,m), 2.1-2.5 (5H,m), 3.6 (3H,s), 3.8-4.3 (2H,m), 6.7 (2H,br s), 7.2 (4H,s); m/e (chemical ionisation): 323 (M+ +H), 340 (M+ +NH4). After 1 hour the solution obtained the mixture was evaporated The residue was partitioned between ether (100 ml.) and saturated sodium bicarbonate solution (50 ml.) extracted thoroughly with ether The combined extracts were washed with water dried (MgSO4) evaporated The residual oil was purified by medium pressure liquid chromatography on silica (190 g.) eluting with 30% v/v ethyl acetate/hexane

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

Procedure: o-Tolylacetic acid (4.56 g.) in THF (50 ml.) was treated at 5°-10° C. under argon with a 1.6M solution (36.0 ml.) of butyllithium in hexane. After 1 hour the solution obtained was added dropwise to a solution of methyl 7-formylheptanoate (5.68 g.) in dry THF (50 ml.) at -30 ° to -50° C. during 30 minutes. The mixture was stirred for 1.5 hours at the same temperature. Acetic acid (3.5 ml. ) was then added carefully and the mixture was evaporated. The residue was partitioned between ether (100 ml.) and saturated sodium bicarbonate solution (50 ml.). The aqueous layer was acidified to pH 4 (HCl) and extracted thoroughly with ether. The combined extracts were washed with water, dried (MgSO4) and evaporated. The residual oil was purified by medium pressure liquid chromatography on silica (190 g.), eluting with 30% v/v ethyl acetate/hexane, to give methyl 9-carboxy-8-hydroxy-9-o-tolylnonanoate (A) as an oil (1.94 g., single diastereoisomer);NMR : 1-1.7 (10H,m), 2.1-2.5 (5H,m), 3.6 (3H,s), 3.8-4.3 (2H,m), 6.7 (2H,br s), 7.2 (4H,s); m/e (chemical ionisation): 323 (M+ +H), 340 (M+ +NH4). After 1 hour the solution obtained the mixture was evaporated The residue was partitioned between ether (100 ml.) and saturated sodium bicarbonate solution (50 ml.) extracted thoroughly with ether The combined extracts were washed with water dried (MgSO4) evaporated The residual oil was purified by medium pressure liquid chromatography on silica (190 g.) eluting with 30% v/v ethyl acetate/hexane

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

Procedure: o-Tolylacetic acid (4.56 g.) in THF (50 ml.) was treated at 5°-10° C. under argon with a 1.6M solution (36.0 ml.) of butyllithium in hexane. After 1 hour the solution obtained was added dropwise to a solution of methyl 7-formylheptanoate (5.68 g.) in dry THF (50 ml.) at -30 ° to -50° C. during 30 minutes. The mixture was stirred for 1.5 hours at the same temperature. Acetic acid (3.5 ml. ) was then added carefully and the mixture was evaporated. The residue was partitioned between ether (100 ml.) and saturated sodium bicarbonate solution (50 ml.). The aqueous layer was acidified to pH 4 (HCl) and extracted thoroughly with ether. The combined extracts were washed with water, dried (MgSO4) and evaporated. The residual oil was purified by medium pressure liquid chromatography on silica (190 g.), eluting with 30% v/v ethyl acetate/hexane, to give methyl 9-carboxy-8-hydroxy-9-o-tolylnonanoate (A) as an oil (1.94 g., single diastereoisomer);NMR : 1-1.7 (10H,m), 2.1-2.5 (5H,m), 3.6 (3H,s), 3.8-4.3 (2H,m), 6.7 (2H,br s), 7.2 (4H,s); m/e (chemical ionisation): 323 (M+ +H), 340 (M+ +NH4). After 1 hour the solution obtained the mixture was evaporated The residue was partitioned between ether (100 ml.) and saturated sodium bicarbonate solution (50 ml.) extracted thoroughly with ether The combined extracts were washed with water dried (MgSO4) evaporated The residual oil was purified by medium pressure liquid chromatography on silica (190 g.) eluting with 30% v/v ethyl acetate/hexane

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Magnesium metal (0.209 g, 8.71 mmol) was added into dry THF (10 ml) in a 50 ml two-necked round bottom flask fitted with a condenser and nitrogen gas inlet. The flask was heated to 70° C., then a few drops of 1,2 dibromoethane were added to the mixture, followed by the slow addition of 1-bromodecane (1.3 g, 5.81 mmol) while at reflux temperature. Stirring was continued for 30 min. After cooling, the Grignard reagent was added dropwise to a stirred solution of methyl 8-oxooctanoate (1.0 g, 5.8 mmol) in THF (10 ml) at −20° C., and the reaction mixture was slowly warmed to room temperature, where stirring was continued for 2 h. The mixture was quenched with saturated ammonium chloride solution, extracted with (3×25 ml) of ethyl acetate, and the combined organic layers were washed with brine solution, dried on anhydrous MgSO4, concentrated and purified on silica gel (2:8 ethyl acetate and hexanes) to obtain an off-white solid (450 mg, 47%). fitted with a condenser and nitrogen gas inlet at reflux temperature After cooling the reaction mixture was slowly warmed to room temperature where stirring was continued for 2 h The mixture was quenched with saturated ammonium chloride solution extracted with (3×25 ml) of ethyl acetate the combined organic layers were washed with brine solution dried on anhydrous MgSO4 concentrated purified on silica gel (2:8 ethyl acetate and hexanes)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Magnesium metal (0.209 g, 8.71 mmol) was added into dry THF (10 ml) in a 50 ml two-necked round bottom flask fitted with a condenser and nitrogen gas inlet. The flask was heated to 70° C., then a few drops of 1,2 dibromoethane were added to the mixture, followed by the slow addition of 1-bromodecane (1.3 g, 5.81 mmol) while at reflux temperature. Stirring was continued for 30 min. After cooling, the Grignard reagent was added dropwise to a stirred solution of methyl 8-oxooctanoate (1.0 g, 5.8 mmol) in THF (10 ml) at −20° C., and the reaction mixture was slowly warmed to room temperature, where stirring was continued for 2 h. The mixture was quenched with saturated ammonium chloride solution, extracted with (3×25 ml) of ethyl acetate, and the combined organic layers were washed with brine solution, dried on anhydrous MgSO4, concentrated and purified on silica gel (2:8 ethyl acetate and hexanes) to obtain an off-white solid (450 mg, 47%). fitted with a condenser and nitrogen gas inlet at reflux temperature After cooling the reaction mixture was slowly warmed to room temperature where stirring was continued for 2 h The mixture was quenched with saturated ammonium chloride solution extracted with (3×25 ml) of ethyl acetate the combined organic layers were washed with brine solution dried on anhydrous MgSO4 concentrated purified on silica gel (2:8 ethyl acetate and hexanes)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Magnesium metal (0.209 g, 8.71 mmol) was added into dry THF (10 ml) in a 50 ml two-necked round bottom flask fitted with a condenser and nitrogen gas inlet. The flask was heated to 70° C., then a few drops of 1,2 dibromoethane were added to the mixture, followed by the slow addition of 1-bromodecane (1.3 g, 5.81 mmol) while at reflux temperature. Stirring was continued for 30 min. After cooling, the Grignard reagent was added dropwise to a stirred solution of methyl 8-oxooctanoate (1.0 g, 5.8 mmol) in THF (10 ml) at −20° C., and the reaction mixture was slowly warmed to room temperature, where stirring was continued for 2 h. The mixture was quenched with saturated ammonium chloride solution, extracted with (3×25 ml) of ethyl acetate, and the combined organic layers were washed with brine solution, dried on anhydrous MgSO4, concentrated and purified on silica gel (2:8 ethyl acetate and hexanes) to obtain an off-white solid (450 mg, 47%). fitted with a condenser and nitrogen gas inlet at reflux temperature After cooling the reaction mixture was slowly warmed to room temperature where stirring was continued for 2 h The mixture was quenched with saturated ammonium chloride solution extracted with (3×25 ml) of ethyl acetate the combined organic layers were washed with brine solution dried on anhydrous MgSO4 concentrated purified on silica gel (2:8 ethyl acetate and hexanes)

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

Procedure: 48 g cyclooctene (1) and 8.4 g sodium bicarbonate were ozonolysed in 48 g methanol and 1 l dichloromethane at −78° C. for 5.5 h. 304 g triethylamine was added slowly dropwise at −60 [lacuna] C and the reaction mixture was allowed to warm to room temperature in the course of 1 h. The reaction mixture was washed with sodium thiosulphate solution (10%, 200 ml), 2 N HCl (150 ml), NaOH (5%, 150 ml) and NaCl solution (saturated, 200 ml) and dried over sodium sulphate and the solvent was distilled off. After distillation, methyl 8-oxooctanoate (2) was obtained. The reaction mixture was washed with sodium thiosulphate solution (10%, 200 ml), 2 N HCl (150 ml), NaOH (5%, 150 ml) and NaCl solution (saturated, 200 ml) dried over sodium sulphate the solvent was distilled off After distillation

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

Procedure: o-Tolylacetic acid (4.56 g.) in THF (50 ml.) was treated at 5°-10° C. under argon with a 1.6M solution (36.0 ml.) of butyllithium in hexane. After 1 hour the solution obtained was added dropwise to a solution of methyl 7-formylheptanoate (5.68 g.) in dry THF (50 ml.) at -30 ° to -50° C. during 30 minutes. The mixture was stirred for 1.5 hours at the same temperature. Acetic acid (3.5 ml. ) was then added carefully and the mixture was evaporated. The residue was partitioned between ether (100 ml.) and saturated sodium bicarbonate solution (50 ml.). The aqueous layer was acidified to pH 4 (HCl) and extracted thoroughly with ether. The combined extracts were washed with water, dried (MgSO4) and evaporated. The residual oil was purified by medium pressure liquid chromatography on silica (190 g.), eluting with 30% v/v ethyl acetate/hexane, to give methyl 9-carboxy-8-hydroxy-9-o-tolylnonanoate (A) as an oil (1.94 g., single diastereoisomer);NMR : 1-1.7 (10H,m), 2.1-2.5 (5H,m), 3.6 (3H,s), 3.8-4.3 (2H,m), 6.7 (2H,br s), 7.2 (4H,s); m/e (chemical ionisation): 323 (M+ +H), 340 (M+ +NH4). After 1 hour the solution obtained the mixture was evaporated The residue was partitioned between ether (100 ml.) and saturated sodium bicarbonate solution (50 ml.) extracted thoroughly with ether The combined extracts were washed with water dried (MgSO4) evaporated The residual oil was purified by medium pressure liquid chromatography on silica (190 g.) eluting with 30% v/v ethyl acetate/hexane