Sodium Hydroxide → tert-butyl (1R,2R)-1-(5-bromo-2-fluoropyridin-3-yl)-2-(3-fluorophenyl)-2-hydroxyethylcarbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of tert-butyl carbamate (363 mg, 3.10 mmol) in propanol (10 mL) was added sodium hydroxide (122 mg, 3.05 mmol) in water (4 mL) followed by tert-butyl hypochlorite (331 mg, 3.05 mmol). After 5 min the solution was cooled to 0° C. and treated with a solution of (DHQD)2PHAL (38.9 mg, 0.050 mmol) in propanol (4 mL). To this solution was added a solution of (E)-5-bromo-2-fluoro-3-(3-fluorostyryl)pyridine (296 mg, 1.0 mmol) in propanol (10 mL). To this solution was added potassium osmate dihydrate (14.73 mg, 0.040 mmol) in one portion. The reaction turned light orange and was allowed to stir at 0° C. for 1 hr. The ice bath was then removed and the reaction was allowed to warm to room temperature and stirred overnight. The reaction was 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-(5-bromo-2-fluoropyridin-3-yl)-2-(3-fluorophenyl)-2-hydroxyethylcarbamate (223 mg, 0.520 mmol, 52.0% yield) along with its regioisomer as an inseparable mixture. LC/Mass spec. (Analytical HPLC method 2): RT=2.11 min. Mass=453.14 (MNa)+.

Provenance & Evidence