Acetic Acid → Tert-butyl 3-(2-(2-bromo-3-methylphenylamino)-2-oxoethyl)piperazine-1-carboxylate

Participants

Reaction Steps

To a solution of 2-(((9H-fluoren-9-yl)methoxy)carbonyl)-4-(tert-butoxycarbonyl)piperazin-2-yl)acetic acid (3.00 g, 6.43 mmol) in dichloromethane (50 mL) with N,N-dimethylformamide (2 drops) was added oxalyl chloride (1.13 mL, 12.9 mmol) drop wise. The reaction mixture was stirred at room temperature for 1 hour, and then it was concentrated. The concentrate is taken up in tetrahydrofuran (50 mL) and 2-bromo-3-methyl aniline (1.33 g, 7.07 mmol) was added in tetrahydrofuran (5 mL) and diisopropylethylamine (5.62 mL, 36.2 mmol). The solution is heated to 70° C. for 2 hours. The mixture was then cooled to 50° C. and piperazine (1.66 g, 19.3 mmol) was added. The reaction mixture stirred for 16 hours before concentration onto silica gel. Purification via flash chromatography (0-20% methanol/dichloromethane) afforded the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 7.54-7.71 (m, 1H), 7.06-7.31 (m, 2H), 3.62-3.98 (m, 2H), 2.26-3.45 (m, 10H), 0.87-1.05 (m, 9H); MS (APCI+) m/z 412, 414 (M+H)+.

Provenance & Evidence