Hydrochloric Acid → (2R)-2-(4-(2-methylpentyloxy)phenyl)-2-((S)-2-phenylpropanamido)ethyl acetate

Participants

Reaction Steps

To a solution of (2R)-2-amino-2-(4-(2-methylpentyloxy)phenyl)ethyl acetate.HCl (400 mg, 1.432 mmol) and (S)-2-phenylpropanoic acid (323 mg, 2.15 mmol) in tetrahydrofuran (8 mL) at 0° C. was added N,N-diisopropylethylamine (0.875 mL, 5.01 mmol) followed by HATU (817 mg, 2.15 mmol). The cooling bath was removed and the mixture was stirred at room temperature under N2 overnight. The reaction mixture was transferred to a separatory funnel containing saturated aqueous NaHCO3 solution (25 mL). The aqueous layer was extracted with ethyl acetate (3×25 mL). The combined organic layers were washed with brine (25 mL), dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (30%→45% ethyl acetate in hexanes; 40 g column) and dried under vacuum to afford (2R)-2-(4-(2-methylpentyloxy)phenyl)-2-((S)-2-phenylpropanamido)ethyl acetate (430 mg, 73.0% yield) as a colorless solid: 1H NMR (400 MHz, CDCl3) δ 7.22-7.37 (m, 5H), 6.95 (d, J=8.6 Hz, 2H), 6.76 (d, J=8.8 Hz, 2H), 5.87 (d, J=8.1 Hz, 1H), 5.16 (td, J=7.7, 4.5 Hz, 1H), 4.25 (dd, J=11.5, 7.4 Hz, 1H), 4.14 (dd, J=11.3, 4.5 Hz, 1H), 3.74 (dd, J=8.8, 5.8 Hz, 1H), 3.65 (dd, J=8.8, 6.8 Hz, 1H), 3.59 (q, J=7.1 Hz, 1H), 1.95 (s, 3H), 1.85-1.95 (m, 1H), 1.49 (d, J=7.3 Hz, 3H), 1.24-1.47 (m, 3H), 1.13-1.23 (m, 1H), 0.97 (d, J=6.8 Hz, 3H), 0.90 (t, J=7.3 Hz, 3H); LRMS (ESI) m/e 412.2 [(M+H)+, calcd for C25H34NO4 412.3].

Provenance & Evidence