4-Fluorobenzylamine → 2-Bromo-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamide

Participants

Reaction Steps

To a solution of 2-bromo-4-methylthiazole-5-carboxylic acid (2.00 g, 9.00 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.41 g, 12.6 mmol) and N,N-diisopropylethylamine (4.67 mL, 27.0 mmol) in tetrahydrofuran (40 mL) was added 1-hydroxybenzotriazole (1.70 g, 12.6 mmol). The resulting mixture was stirred at ambient temperature for 30 minutes and 4-fluorobenzylamine (1.43 mL, 12.6 mmol) was added. The reaction mixture was kept stirring at ambient temperature for 17 hours, then concentrated in vacuo. The residue was dissolved ethyl acetate and washed with water and brine. The organic solution was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography to afford 2-bromo-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamide in 81% yield (2.38 g): 1H NMR (300 MHz, CDCl3) δ 7.30-7.26 (m, 2H), 7.05-7.00 (m, 2H), 5.99-5.87 (m, 1H), 4.54 (d, J=5.7 Hz, 2H), 2.63 (s, 3H).

Provenance & Evidence