To a solution of tert-butyl carbamate (83 g, 709 mmol) in 1-propanol (780 mL) was added 0.5 M of aqueous sodium hydroxide (1418 mL, 709 mmol), followed by tert-butyl hypochlorite (77 g, 709 mmol) (internal temperature 28.2° C.). The reaction mixture was stirred at ambient temperature for 10 min. To this reaction mixture was added (DHQD)2PHAL (5.52 g, 7.09 mmol) and 1-propanol (780 mL), followed by (E)-3-bromo-5-(2,5-difluorostyryl)pyridine (70.0 g, 236 mmol) and 1-propanol (780 mL). This white mixture was cooled to 0° C. with a methanol/ice bath. Then potassium osmate dihydrate (2.61 g, 7.09 mmol) was added to this mixture. After 30 min of stirring, the ice bath was removed. The reaction was stirred at room temperature overnight. After 16 h, the reaction mixture was partitioned with water (1 L) and EtOAc (2.4 L). The organic layer was washed with 5% sodium sulfite three times (Note: Each wash was mechanically stirred for 10 min to ensure reduction of osmium. The first two washes were dark; the third wash was clear. The organic layer was washed with brine (3×500 mL), dried (sodium sulfate), filtered, and concentrated to give 136 g of crude tert-butyl((1R,2R)-1-(5-bromopyridin-3-yl)-2-(2,5-difluorophenyl)-2-hydroxyethyl)carbamate and tert-butyl((1R,2R)-2-(5-bromopyridin-3-yl)-1-(2,5-difluorophenyl)-2-hydroxyethyl)carbamate (ca. 6:1 ratio). LC/MS (ES+) 430.9 (M+H, 100).
