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

Participants

Reaction Steps

To a solution of of 2-bromo-4-methylthiazole-5-carboxylic acid (9.00 g, 40.0 mmol) in anhydrous tetrahydrofuran (140 mL) was added N,N-diisopropylethylamine (20.76 mL, 121.0 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (10.87 g, 56.0 mmol). The reaction mixture was stirred at ambient temperature for 0.5 hours and 1-hydroxybenzotriazole (7.60 g, 56.0 mmol) and benzyl amine (6.00 g, 56.0 mmol) were added. The resulting mixture was stirred at ambient temperature for 18 hours, then concentrated to half volume in vacuo, diluted with dichloromethane (400 mL), and washed with water (400 mL) and brine (150 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluted with ethyl acetate/hexane (1/1) to afford the title compound as a colorless solid in 70% yield (8.89 g): mp 92-94° C. (ethyl acetate/hexanes); 1H NMR (300 MHz, CDCl3) δ 7.41-7.23 (m, 5H), 5.94 (br s, 1H), 4.57 (d, J=5.6 Hz, 2H), 2.64 (s, 3H); MS (ES+) m/z 311.0 (M+1), 313.1 (M+3).

Provenance & Evidence