Acetic Acid → (R)-N-(2-chloro-5-((1-(3-chlorophenyl)ethylamino)methyl)phenyl)-5-methylisoxazole-3-carboxamide

Participants

Reaction Steps

To a solution of N-(2-chloro-5-formylphenyl)-5-methylisoxazole-3-carboxamide 3 (0.117 g, 0.44 mmol) in DCE (3 mL) was added (R)-1-(3-chlorophenyl)ethanamine (0.079 g, 0.51 mmol), acetic acid (0.030 mL, 0.52 mmol), and NaBH(OAc)3 (0.108 g, 0.51 mmol). The reaction mixture was stirred at room temperature for 16 h and diluted with EtOAc. The organic phase was washed with saturated NaHCO3 (1×), brine (1×), dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash column chromatography on silica gel (eluted with 20% to 60% EtOAc in hexanes) gave (R)—N-(2-chloro-5-((1-(3-chlorophenyl)ethylamino)methyl)phenyl)-5-methylisoxazole-3-carboxamide 4 (0.131 g, 73% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 1.36 (d, J=6.5 Hz, 3H), 2.53 (s, 3H), 3.60 (d, J=13.7 Hz, 1H), 3.66 (d, J=13.7 Hz, 1H), 3.79 (q, J=6.5 Hz, 1H), 6.53 (s, 1H), 7.04 (d, J=8.2 Hz, 1H), 7.21-7.36 (m, 6H), 8.41 (s, 1H), 9.10 (s br, 1H). Mass spectrum: calculated for C20H19Cl2N3O2 403.1. found 404.1 (M++1).

Provenance & Evidence