ethyl 4,4-difluoro-3-oxopentanoate

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl 4,4-difluoro-3-oxo-pentanoate (12.4 g, 0.068 mmol) was dissolved in toluene (100 ml) and cooled to 0° C. Sodium borohydride (3.12 g, 0.083 g) was added portionwise, and the mixture was allowed to reach room temperature overnight with stirring. The mixture was then cooled to 0° C. and acidified with 1 m HCl. The phases were separated, the aqueous phase was extracted two times with ethyl acetate, the combined organic phases were dried over magnesium sulfate and the solvent was removed under reduced pressure. The residue was dissolved in a minimum amount of methanol, the resulting solution was evaporated to dryness under reduced pressure to yield 8.76 g of a residue (0.048 mol, 70%) that were used directly in the next step. The mixture was then cooled to 0° C. The phases were separated the aqueous phase was extracted two times with ethyl acetate the combined organic phases were dried over magnesium sulfate the solvent was removed under reduced pressure The residue was dissolved in a minimum amount of methanol the resulting solution was evaporated to dryness under reduced pressure

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl 4,4-difluoro-3-oxo-pentanoate (12.4 g, 0.068 mmol) was dissolved in toluene (100 ml) and cooled to 0° C. Sodium borohydride (3.12 g, 0.083 g) was added portionwise, and the mixture was allowed to reach room temperature overnight with stirring. The mixture was then cooled to 0° C. and acidified with 1 m HCl. The phases were separated, the aqueous phase was extracted two times with ethyl acetate, the combined organic phases were dried over magnesium sulfate and the solvent was removed under reduced pressure. The residue was dissolved in a minimum amount of methanol, the resulting solution was evaporated to dryness under reduced pressure to yield 8.76 g of a residue (0.048 mol, 70%) that were used directly in the next step. The mixture was then cooled to 0° C. The phases were separated the aqueous phase was extracted two times with ethyl acetate the combined organic phases were dried over magnesium sulfate the solvent was removed under reduced pressure The residue was dissolved in a minimum amount of methanol the resulting solution was evaporated to dryness under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Lithium hexamethyldisilazide (150 ml of a 1M solution in THF, 0.15 mol) was cooled in an argon athmosphere to −78° C. and ethyl acetate (15 ml, 0.14 mol) was added dropwise with stirring. Stirring was continued for one hour at −78° C., then ethyl 2,2-difluoropropionate (12 g, 0.089 mol) was added dropwise with stirring. Stirring was continued for four hours at −78° C., then a saturated solution of ammonium chloride (175 ml) was added dropwise. The mixture was allowed to reach room temperature, acidified with 1M HCl (50 ml) and left standing overnight. The phases were separated. The aqueous phase was extracted with ethyl acetate, the combined organic phases were washed with 1M HCl, brine, dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by vacuum distillation (54 mbar, 130° C.) to yield 12.4 g (0.068 mmol, 77%) of a colourless liquid that was used directly in the next step. Stirring with stirring Stirring was continued for four hours at −78° C. to reach room temperature left standing overnight The phases were separated The aqueous phase was extracted with ethyl acetate the combined organic phases were washed with 1M HCl, brine dried over sodium sulfate The solvent was removed under reduced pressure the residue was purified by vacuum distillation (54 mbar, 130° C.)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl 4,4-difluoro-3-oxo-pentanoate (12.4 g, 0.068 mmol) was dissolved in toluene (100 ml) and cooled to 0° C. Sodium borohydride (3.12 g, 0.083 g) was added portionwise, and the mixture was allowed to reach room temperature overnight with stirring. The mixture was then cooled to 0° C. and acidified with 1M HCl. The phases were separated, the aqueous phase was extracted two times with ethyl acetate, the combined organic phases were dried over magnesium sulfate and the solvent was removed under reduced pressure. The residue was dissolved in a minimum amount of methanol, the resulting solution was evaporated to dryness under reduced pressure to yield 8.76 g of a residue (0.048 mol, 70%) that were used directly in the next step. The mixture was then cooled to 0° C. The phases were separated the aqueous phase was extracted two times with ethyl acetate the combined organic phases were dried over magnesium sulfate the solvent was removed under reduced pressure The residue was dissolved in a minimum amount of methanol the resulting solution was evaporated to dryness under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Lithium hexamethyldisilazide (150 ml of a 1M solution in THF, 0.15 mol) was cooled in an argon atmosphere to −78° C. and ethyl acetate (15 ml, 0.14 mol) was added dropwise with stirring. Stirring was continued for one hour at −78° C., then ethyl 2,2-difluoropropionate (12 g, 0.089 mol) was added dropwise with stirring. Stirring was continued for four hours at −78° C., then a saturated solution of ammonium chloride (175 ml) was added dropwise. The mixture was allowed to reach room temperature, acidified with 1M HCl (50 ml) and left standing overnight. The phases were separated. The aqueous phase was extracted with ethyl acetate, the combined organic phases were washed with 1M HCl, brine and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by vacuum distillation (54 mbar, 130° C.) to yield 12.4 g (0.068 mmol, 77%) of a colourless liquid that was used directly in the next step. Stirring with stirring Stirring was continued for four hours at −78° C. to reach room temperature left standing overnight The phases were separated The aqueous phase was extracted with ethyl acetate the combined organic phases were washed with 1M HCl, brine dried over sodium sulfate The solvent was removed under reduced pressure the residue was purified by vacuum distillation (54 mbar, 130° C.)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl 4,4-difluoro-3-oxo-pentanoate (12.4 g, 0.068 mmol) was dissolved in toluene (100 ml) and cooled to 0° C. Sodium borohydride (3.12 g, 0.083 g) was added portionwise, and the mixture was allowed to reach room temperature overnight with stirring. The mixture was then cooled to 0° C. and acidified with 1 m HCl. The phases were separated, the aqueous phase was extracted two times with ethyl acetate, the combined organic phases were dried over magnesium sulfate and the solvent was removed under reduced pressure. The residue was dissolved in a minimum amount of methanol, the resulting solution was evaporated to dryness under reduced pressure to yield 8.76 g of a residue (0.048 mol, 70%) that were used directly in the next step. The mixture was then cooled to 0° C. The phases were separated the aqueous phase was extracted two times with ethyl acetate the combined organic phases were dried over magnesium sulfate the solvent was removed under reduced pressure The residue was dissolved in a minimum amount of methanol the resulting solution was evaporated to dryness under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Lithium hexamethyldisilazide (150 ml of a 1M solution in THF, 0.15 mol) was cooled in an argon athmosphere to −78° C. and ethyl acetate (15 ml, 0.14 mol) was added dropwise with stirring. Stirring was continued for one hour at −78° C., then ethyl 2,2-difluoropropionate (12 g, 0.089 mol) was added dropwise with stirring. Stirring was continued for four hours at −78° C., then a saturated solution of ammonium chloride (175 ml) was added dropwise. The mixture was allowed to reach room temperature, acidified with 1M HCl (50 ml) and left standing overnight. The phases were separated. The aqueous phase was extracted with ethyl acetate, the combined organic phases were washed with 1M HCl, brine, dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by vacuum distillation (54 mbar, 130° C.) to yield 12.4 g (0.068 mmol, 77%) of a colourless liquid that was used directly in the next step. Stirring with stirring Stirring was continued for four hours at −78° C. to reach room temperature left standing overnight The phases were separated The aqueous phase was extracted with ethyl acetate the combined organic phases were washed with 1M HCl, brine dried over sodium sulfate The solvent was removed under reduced pressure the residue was purified by vacuum distillation (54 mbar, 130° C.)