Sodium Hydroxide → tert-butyl (1R,2R)-1-(2-bromo-5-fluoropyridin-4-yl)-2-(4-fluorophenyl)-2-hydroxyethylcarbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of tert-butyl carbamate (189 mg, 1.612 mmol) in propanol (4 mL) was added sodium hydroxide (54.1 mg, 1.352 mmol) in water (2 mL) followed by tert-butyl hypochlorite (172 mg, 1.586 mmol). After 5 min the solution was cooled to 0° C. and treated with a solution of (DHQD)2PHAL (20.26 mg, 0.026 mmol) in propanol (1 mL). To this solution was added a solution of (E)-2-bromo-5-fluoro-4-(4-fluorostyryl)pyridine (154 mg, 0.520 mmol) in propanol (7 mL). To this solution was added potassium osmate dihydrate (7.66 mg, 0.021 mmol) dissolved in water (3 mL) in one portion. The reaction turned light orange and was allowed to stir at 0° C. overnight. The reaction was complete the next morning after warming to room temperature. The reaction was then quenched with a 10% solution of sodium thiosulfate and stirred for 30 min. The reaction was then extracted with diethylether (3×). The combined organic extracts were combined washed with water, then brine. The organic layer was separated, dried over sodium sulfate and evaporated in vacuo. The crude residue was purified by silica gel chromatography 25% EtOAc/75% Hexanes to 50%/50% EtOAc/Hexanes to afford tert-butyl (1R,2R)-1-(2-bromo-5-fluoropyridin-4-yl)-2-(4-fluorophenyl)-2-hydroxyethylcarbamate (56 mg, 0.130 mmol, 62.7% yield) along with its regioisomer as an inseparable mixture. LC/Mass spec. (Analytical HPLC method 2): RT=2.09 min. Mass=431.05 (MH)+.

Provenance & Evidence