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

Participants

Reaction Conditions

Reaction Steps

To tert-butyl carbamate (206 mg, 1.76 mmol) in propanol (1 mL) was added sodium hydroxide (69.1 mg, 1.73 mmol) in water (1.9 mL) followed by tert-butyl hypochlorite (0.195 mL, 1.73 mmol). After 5 min, the solution was cooled to 0° C. and treated with a solution of (DHQD)2PHAL (22.1 mg, 0.028 mmol) in propanol (0.9 mL). The reaction was diluted with propanol (1.25 mL) and treated with (E)-2-bromo-4-(2,5-difluorostyryl)-5-fluoropyridine (89 mg, 0.28 mmol) as a solid in one portion. To this was added potassium osmate dihydrate (8.4 mg, 0.023 mmol) as a solid in one portion. The reaction was allowed to gradually warm to room temperature in the dewar over 8 h. The reaction was cooled to 0° C. and quenched by addition of sodiumthiosulfate (210 mg) in water (1 mL). The reaction was stirred at room temperature for 30 min. The reaction was extracted with ether (2×). The ethereal was washed with water (2×), then brine, dried over magnesium sulfate, and concentrated to give a solid (quant.). The material was used without purification. Mass spec.: 447.1 (MH)+.

Provenance & Evidence