甲基 3,3-二甲基-5-氧代戊酸乙酯

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (S)-(3,5-bis-trifluoromethyl-benzyl)-(3,5,6,7,8,9-hexahydro-1H-2-oxa-5-aza-cyclohepta[f]inden-9-yl)-(2-methyl-2H-tetrazol-5-yl)-amine (0.195 mmol) in dichloroethane (5 mL), add 3,3-dimethyl-5-oxo-pentanoic acid methyl ester (0.585 mmol) along with a catalytic amount of acetic acid. To this stirred solution add sodium triacetoxyborohydride (0.975 mmol). After stirring for 12 h, quench the reaction with aqueous sodium carbonate (5 mL) and dilute with dichloromethane (5 mL). Dry the organic portion, filter, and remove the solvent under vacuum. Chromatograph the product over silica gel, eluting with ethyl acetate/hexane (2-35%) to afford the title compound as a colorless oil. MS (ES+): 655.2 (M+H). quench the reaction with aqueous sodium carbonate (5 mL) Dry the organic portion filter remove the solvent under vacuum Chromatograph the product over silica gel, eluting with ethyl acetate/hexane (2-35%)

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To an agitated mixture of methyl 3,3-dimethyl-5-oxopentanoate (1.0 g), 1,1-dichloro-2,2,2-trifluoroethane (1.06 g) and dry tetrahydrofuran (10 cm3), maintained at -78° C., was added, over a period of 5 minutes, sodium t-butoxide (1.66 cm3 of a 42% w/w solution in dimethylformamide) after which the mixture continued to be agitated at -78° C. for a further 60 minutes. The reaction was quenched with saturated ammonium chloride at low temperature and the mixture allowed to warm to the ambient temperature. After addition of water (20 cm3) and separation of the organic phase, the aqueous phase was extracted with di-isopropyl ether (3×30 cm3) and the extracts combined with the organic phase, which was washed with brine (2×10 cm3) and dried over anhydrous magnesium sulphate. After removal of the volatile components by evaporation under reduced pressure the residual oil was purified by column chromatography (silica gel column eluted with a 9:1 mixture (by volume) of hexane and ethyl acetate) to give methyl 6,6-dichloro-3,3-dimethyl-5-hydroxy-7,7,7-trifluoroheptanoate as a colourless oil (yield 56%). was added, over a period of 5 minutes The reaction was quenched with saturated ammonium chloride at low temperature to warm to the ambient temperature After addition of water (20 cm3) and separation of the organic phase the aqueous phase was extracted with di-isopropyl ether (3×30 cm3) was washed with brine (2×10 cm3) dried over anhydrous magnesium sulphate After removal of the volatile components by evaporation under reduced pressure the residual oil was purified by column chromatography (silica gel column eluted with a 9:1 mixture (by volume) of hexane and ethyl acetate)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of methyl 5-bromo-3,3-dimethylpentanoate (5.0 g), pyridine-N-oxide (4.49 g), sodium bicarbonate (3.77 g) and toluene (30 cm3) was heated at the reflux temperature with vigorous agitation for a period of 14 hours. After cooling the mixture to the ambient temperature, water (20 cm3), saturated ammonium carbonate solution (20 cm3) and toluene (50 cm3) were added and the aqueous phase separated and extracted with toluene (3×75 cm3). The toluene extracts were added to the main organic phase and the whole dried over anhydrous magnesium sulphate concentrated by evaporation of the more volatile components under reduced pressure. The residual liquid was purified by Kugelrohr distillation (130° C./water pump pressure) to give methyl 3,3-dimethyl-5-oxopentanoate in 63% yield. was heated at the reflux temperature with vigorous agitation for a period of 14 hours were added the aqueous phase separated extracted with toluene (3×75 cm3) The toluene extracts were added to the main organic phase the whole dried over anhydrous magnesium sulphate concentrated by evaporation of the more volatile components under reduced pressure The residual liquid was purified by Kugelrohr distillation (130° C./water pump pressure)

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To an agitated mixture of methyl 3,3-dimethyl-5-oxopentanoate (1.0 g), 1,1-dichloro-2,2,2-trifluoroethane (1.06 g) and dry tetrahydrofuran (10 cm3), maintained at -78° C., was added, over a period of 5 minutes, sodium t-butoxide (1.66 cm3 of a 42% w/w solution in dimethylformamide) after which the mixture continued to be agitated at -78° C. for a further 60 minutes. The reaction was quenched with saturated ammonium chloride at low temperature and the mixture allowed to warm to the ambient temperature. After addition of water (20 cm3) and separation of the organic phase, the aqueous phase was extracted with di-isopropyl ether (3×30 cm3) and the extracts combined with the organic phase, which was washed with brine (2×10 cm3) and dried over anhydrous magnesium sulphate. After removal of the volatile components by evaporation under reduced pressure the residual oil was purified by column chromatography (silica gel column eluted with a 9:1 mixture (by volume) of hexane and ethyl acetate) to give methyl 6,6-dichloro-3,3-dimethyl-5-hydroxy-7,7,7-trifluoroheptanoate as a colourless oil (yield 56%). was added, over a period of 5 minutes The reaction was quenched with saturated ammonium chloride at low temperature to warm to the ambient temperature After addition of water (20 cm3) and separation of the organic phase the aqueous phase was extracted with di-isopropyl ether (3×30 cm3) was washed with brine (2×10 cm3) dried over anhydrous magnesium sulphate After removal of the volatile components by evaporation under reduced pressure the residual oil was purified by column chromatography (silica gel column eluted with a 9:1 mixture (by volume) of hexane and ethyl acetate)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of methyl 5-bromo-3,3-dimethylpentanoate (5.0 g), pyridine-N-oxide (4.49 g), sodium bicarbonate (3.77 g) and toluene (30 cm3) was heated at the reflux temperature with vigorous agitation for a period of 14 hours. After cooling the mixture to the ambient temperature, water (20 cm3), saturated ammonium carbonate solution (20 cm3) and toluene (50 cm3) were added and the aqueous phase separated and extracted with toluene (3×75 cm3). The toluene extracts were added to the main organic phase and the whole dried over anhydrous magnesium sulphate concentrated by evaporation of the more volatile components under reduced pressure. The residual liquid was purified by Kugelrohr distillation (130° C./water pump pressure) to give methyl 3,3-dimethyl-5-oxopentanoate in 63% yield. was heated at the reflux temperature with vigorous agitation for a period of 14 hours were added the aqueous phase separated extracted with toluene (3×75 cm3) The toluene extracts were added to the main organic phase the whole dried over anhydrous magnesium sulphate concentrated by evaporation of the more volatile components under reduced pressure The residual liquid was purified by Kugelrohr distillation (130° C./water pump pressure)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of (S)-(3,5-bis-trifluoromethyl-benzyl)-(3,5,6,7,8,9-hexahydro-1H-2-oxa-5-aza-cyclohepta[f]inden-9-yl)-(2-methyl-2H-tetrazol-5-yl)-amine (0.195 mmol) in dichloroethane (5 mL), add 3,3-dimethyl-5-oxo-pentanoic acid methyl ester (0.585 mmol) along with a catalytic amount of acetic acid. To this stirred solution add sodium triacetoxyborohydride (0.975 mmol). After stirring for 12 h, quench the reaction with aqueous sodium carbonate (5 mL) and dilute with dichloromethane (5 mL). Dry the organic portion, filter, and remove the solvent under vacuum. Chromatograph the product over silica gel, eluting with ethyl acetate/hexane (2-35%) to afford the title compound as a colorless oil. MS (ES+): 655.2 (M+H). quench the reaction with aqueous sodium carbonate (5 mL) Dry the organic portion filter remove the solvent under vacuum Chromatograph the product over silica gel, eluting with ethyl acetate/hexane (2-35%)