ethyl 2,2-difluoro-4-phenylbutanoate

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

Procedure: To a cooled solution of Intermediate 1 (1.0 g, 4.45 mmol) in tetrahydrofuran (15 mL) was added lithium aluminum hydride (0.22 g, 5.78 mmol). The mixture was stirred at room temperature overnight. To the crude reaction was added water (0.3 mL), 4N sodium hydroxide (0.3 ml) and water (0.9 mL). The resulting solid was filtered through Celite and the solvent removed under reduced pressure. The residue was diluted with methylene chloride (20 mL) and washed with water (10 mL), 2N hydrochloric acid (2×10 mL) and water (10 mL), dried (Na2SO4), and concentrated. The title compound was obtained as brown oil (0.6 g, 72%). To the crude reaction The resulting solid was filtered through Celite the solvent removed under reduced pressure The residue was diluted with methylene chloride (20 mL) washed with water (10 mL), 2N hydrochloric acid (2×10 mL) and water (10 mL) dried (Na2SO4) concentrated

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

Procedure: 2,2-Difluoro-4-phenyl-butyric acid ethyl ester (0.23 g, 1 mmol) was dissolved in EtOH (4 ml) and treated with NaBH4 (39.4 mg, 1 mmol). After 30 minutes stirring at room temperature, the reaction mixture was cooled to 0° C., acidified to pH 1 with 1N HCl (2 ml), diluted with H2O (10 ml). The aqueous phase was extracted with ether (3 times). The combined organic phases were dried over Na2SO4, filtered and the solvent was removed in vacuo. The residue was chromatographed over silica gel (hexane-ethylacetate 99:1) to provide 2,2-difluoro-4-phenyl-butan-1-ol (0.11 g, 58%) as light yellow oil, MS: m/e=186.1 (M+). the reaction mixture was cooled to 0° C. The aqueous phase was extracted with ether (3 times) The combined organic phases were dried over Na2SO4 filtered the solvent was removed in vacuo The residue was chromatographed over silica gel (hexane-ethylacetate 99:1)