Trifluoroacetic acid → HCID 86638156, compound

Participants

Reaction Steps

Add via syringe 1M BH3-THF (78 mL, 78 mmol) to a solution of N—[(S)-1-(5-bromo-pyridin-2-yl)-pyrrolidin-3-yl]-2,2-difluoro-acetamide (8.3 g, 25 mmol) in tetrahydrofuran (65 mL) and heat the mixture at reflux overnight. Cool the reaction to 0° C. and slowly quench with 5N NaOH until no gas evolution is observed. Concentrate the material in vacuo to remove THF. Dilute the residue with water (150 mL) and extract with CH2Cl2 (3×150 mL). Dry the combined organics over Na2SO4, filter, and concentrate to dryness. Add sodium triacetoxyborohydride (35.4 g, 167 mmol) to the residue in dichloromethane (75 mL). Add dropwise trifluoroacetic acid (150 mL) with vigorous stirring. After 10 min concentrate the mixture in vacuo and dilute with CH2Cl2 (150 mL). Cool the mixture in an ice bath and slowly basify to pH 9 with 5N NaOH. Stir the basic mixture overnight. Dilute the mixture with water (200 mL) and extract with CH2Cl2 (3×150 mL). Dry the combined organics over Na2SO4, filter, and concentrate to dryness. Purify by chromatography to afford 6.38 g (85%) of the title compound. MS/ES m/z (79Br) 306.0 [M+H]+.

Provenance & Evidence