Acetyl chloride → (2R)-2-(t-butoxycarbonylamino)-2-(4-(2-methylpentyloxy)phenyl)ethyl acetate

Participants

Reaction Steps

To a solution of (1R)-2-hydroxy-1-(4-(2-methylpentyloxy)phenyl)ethylcarbamate (5.00 g, 14.82 mmol) and triethylamine (10.33 mL, 74.1 mmol) in tetrahydrofuran (50 mL) at 0° C. was added DMAP (1.99 g, 16.30 mmol). Acetyl chloride (4.21 mL, 59.3 mmol) was then added slowly via syringe. After the addition was complete, the cooling bath was removed and the mixture was stirred at room temperature under N2 for 2 h. The reaction mixture was transferred to a separatory funnel containing saturated aqueous NaHCO3 solution (50 mL). The aqueous layer was extracted with ethyl acetate (3×100 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 (15%→25% ethyl acetate in hexanes) to afford (2R)-2-(tert-butoxycarbonylamino)-2-(4-(2-methylpentyloxy)phenyl)ethyl acetate (5.50 g, 98% yield) as a colorless amorphous solid: 1H NMR (400 MHz, DMSO-d6) δ 7.44 (d, J=9.1 Hz, 1H), 7.23 (d, J=8.8 Hz, 2H), 6.88 (d, J=8.6 Hz, 2H), 4.67-4.78 (m, 1H), 4.10 (dd, J=10.8, 5.3 Hz, 1H), 3.98 (dd, J=10.6, 9.1 Hz, 1H), 3.80 (dd, J=9.6, 6.0 Hz, 1H), 3.71 (dd, J=9.3, 6.8 Hz, 1H), 1.97 (s, 3H), 1.86 (dq, J=12.8, 6.5 Hz, 1H), 1.37 (s, 9 H), 1.22-1.47 (m, 3H), 1.11-1.22 (m, 1H), 0.96 (d, J=6.8 Hz, 3H), 0.88 (t, J=7.2 Hz, 3H); LRMS (ESI) m/e 380.3 [(M+H)+, calcd for C21H34NO5 380.3].

Provenance & Evidence