Benzylamine → 2-Bromo-4-methyl-thiazole-5-carboxylic acid benzylamide

Participants

Reaction Steps

Part A. To a solution of 2-bromo-4-methyl-thiazole-5-carboxylic acid (10.0 g, 45.0 mmol, 1.0 equiv) and diisopropylethylamine (15.6 mL, 90.0 mmol, 2.0 equiv) in anhydrous dichloromethane (400 mL) was added benzotriazol-1-yloxytris-(dimethylamino)phosphonium hexafluorophosphate (BOP reagent, 22.0 g, 49.5 mmol, 1.1 equiv) and benzylamine (5.4 mL, 49.5 mmol, 1.1 equiv). The resulting mixture was stirred at ambient temperature for 12 hr. The reaction was diluted with dichloromethane, washed with water, brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by column chromatography [SiO2, ethyl acetate/hexanes, 10:90 to 35:65, v/v]. Further purification by stirring in pentane then filtration afforded 2-bromo-4-methyl-thiazole-5-carboxylic acid benzylamide (9.0 g, 64% yield). 1H NMR (400 MHz, DMSO-d6) δ 8.84 (bs, 1H), 7.23-7.36 (m, 5H), 4.42 (d, J=8.0 Hz, 2H), 2.55 (s, 3H); MS (M+H)+=312.1, Rt=1.32 min.

Provenance & Evidence