2-BROMO-3-METHYLBENZAMIDE synthesis

Yield:101421-85-6 80%

Reaction Conditions:

Stage #1: 3-methyl-2-bromobenzoic acidwith triethylamine;isobutyl chloroformate in dichloromethane at 0 - 20; for 0.5 h;
Stage #2: with ammonium hydroxide in dichloromethane;water at 0; for 0.5 h;

Steps:

Step 1 : To a solution of compound 247 (15 g, 69.8 mmol) in CH2CI2 (100 mL) was added TEA (7.76 g, 76.7 mol) and /^'so-butylchloroformate (10.4 g, 76.7 mmol) at 0 °C. After the addition, the mixture was stirred at 0 °C for 30 minutes, TLC (CH₂CI₂ / MeOH = 10:1 ) showed the reaction was completed. Then, ΝΗ₃·Η₂0 (27.9 g, 0.28 mol, 35% in H₂0) was added to the mixture 0 °C. The resulting mixture was stirred at this temperature for 30 minutes. TLC (petroleum ether / EtOAc = 8:1 ) showed the reaction was completed. The mixture was poured into ice-water (200 mL). The solid was filtered and the wet cake was washed with H₂0 (50 mL), dried to give compound 248 (12 g, 80%) as a white solid. ¹ H NMR (400 MHz, DMSO-d₆) δ 7.70 (brs, 1 H), 7.55 (brs, 1 H), 7.35 (m, 1 H), 7.30 (m, 1 H), 7.15 (m, 1 H), 2.38 (s, 3H).

References:

WO2013/132376,2013,A1 Location in patent:Page/Page column 226