Lithium Chloride → t-butyl (1R)-2-hydroxy-1-(4-(2-methylpentyloxy)phenyl)ethylcarbamate

Participants

Reaction Conditions

Reaction Steps

To a suspension of sodium borohydride (1.346 g, 35.6 mmol) in ethanol (50 mL) at 0° C. was added lithium chloride (1.508 g, 35.6 mmol). The mixture was stirred at 0° C. for 10 min. A solution of (2R)-methyl 2-(tert-butoxycarbonylamino)-2-(4-(2-methylpentyloxy)phenyl)acetate (5.00 g, 13.68 mmol) in tetrahydrofuran (50.0 mL) was then added via cannula. The reaction mixture was warmed up to room temperature and was stirred at room temperature for 3 h. The reaction mixture was cooled to 0° C. and was quenched by the slow addition of saturated aqueous NH4Cl solution (30 mL). The reaction mixture was transferred to a separatory funnel containing water (50 mL). The aqueous layer was extracted with ethyl acetate (3×150 mL). The combined organic layers were washed with brine (50 mL), dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (30%→45% ethyl acetate in hexanes) to afford t-butyl (1R)-2-hydroxy-1-(4-(2-methylpentyloxy)phenyl)ethylcarbamate (4.24 g, 92% yield) as a colorless solid: 1H NMR (400 MHz, DMSO-d6) δ 7.17 (d, J=8.6 Hz, 2H), 7.12 (d, J=8.3 Hz, 1H), 6.84 (d, J=8.6 Hz, 2H), 4.72 (t, J=5.8 Hz, 1H), 4.44 (q, J=6.8 Hz, 1H), 3.79 (dd, J=9.3, 5.8 Hz, 1H), 3.70 (dd, J=9.3, 6.5 Hz, 1H), 3.37-3.49 (m, 2H), 1.80-1.92 (m, 1H), 1.36 (s, 9H), 1.23-1.47 (m, 3H), 1.13-1.21 (m, 1 H), 0.95 (d, J=6.5 Hz, 3H), 0.88 (t, J=7.1 Hz, 3H); LRMS (ESI) m/e 338.2 [(M+H)+, calcd for C19H32NO4 338.2].

Provenance & Evidence