A solution of tert-butyl carbamate (4.18 g, 35.0 mmol) in propanol (39 ml) was sequentially treated with sodium hydroxide (1.376 g, 34.4 mmol) in water (72 ml) and tert-butyl hypochlorite (3.88 ml, 34.4 mmol). After 5 min of stirring, the reaction mixture was cooled to 0° C. A solution of (DHQD)2PHAL (0.555 g, 0.677 mmol) in propanol (39 ml), a solution of (E)-3-bromo-5-(2,5-difluorostyryl)pyridine (3.34 g, 11.28 mmol) in propanol (68 ml), and potassium osmate dihydrate (0.166 g, 0.451 mmol) were sequentially added. The reaction mixture was stirred for three additional hours at 0° C., warmed to ambient temperature and after an additional 16 hours the light yellow homogenous solution was quenched with saturated aqueous sodium sulfite (100 mL). The aqueous phase was extracted with ethyl acetate (2×50 mL), the combined organic phases were washed with brine (100 mL), dried over anhydrous magnesium sulfate and concentrated to afford a residue which was purified via column chromatography (25% to 40% EtOAc/Hex) to provide tert-butyl (1R,2R)-1-(5-bromopyridin-3-yl)-2-(2,5-difluorophenyl)-2-hydroxyethylcarbamate (2.2991 g, 5.09 mmol, 45.1% yield) as an optically enriched mixture of enantiomers. 1H NMR (500 MHz, DMSO-d6) δ 8.56 (d, J=1.8 Hz, 1H), 8.40 (s, 1H), 8.03 (s, 1H), 7.52 (d, J=9.5 Hz, 1H), 7.25 (br. s., 1H), 7.10 (t, J=5.6 Hz, 2H), 5.89 (d, J=4.9 Hz, 1H), 5.03 (t, J=5.0 Hz, 1H), 4.83 (dd, J=8.9, 5.2 Hz, 1H), 1.40-1.34 (m, 9H), MS Anal. Calcd. for [M+H]+ C18H20BrF2N2O3: 429.1. found 431.3.
