Benzoic acid, 2-[[(2'-cyano[1,1'-biphenyl]-4-yl)methyl]amino]-3-nitro-methyl ester

Chemical Properties

Uses

Synthesis

139481-38-2

139481-28-0

30.1 g of methyl 2-((tert-butoxycarbonyl)((2'-cyano-[1,1'-biphenyl]-4-yl)methyl)amino)-3-nitrobenzoate [BAN], 40.8 g of potassium carbonate, and 160 ml of acetonitrile were mixed, and the reaction system may have contained unreacted 2-(4-methylphenyl)benzylcarbonitrile [MPB] and, as a by-product, 2-(4,4-dibromomethylphenyl) benzyl cyanide. The reaction was stirred at 82°C for 5 hours. After completion of the reaction, it was cooled to room temperature, the precipitated crystals were collected by filtration and the filtrate was concentrated to give methyl 2-[N-tert-butoxycarbonyl-N-[(2'-cyanobiphenyl-4-yl)methyl]amino]-3-nitrobenzoate [BBN]. The concentrate was dissolved in 190 g of methanol and 106 g of concentrated hydrochloric acid was added slowly and dropwise. The reaction solution was heated to reflux temperature and kept at reflux stirring for 2 hours. After cooling, the precipitated crystals were collected by filtration and dropwise addition to give 35.1 g of methyl 2-[N-(2'-cyanobiphenyl-4-yl)methylamino]-3-nitrobenzoate [MBN] in 76.1% yield (based on 2-(4-methylphenyl)benzonitrile [MPB]). In Reference Example 4 (2), the resulting concentrate (BBN) was mixed with 3200 L of methanol at 30°C or lower and 1050 L of 35% concentrated hydrochloric acid was added over about 4 hours. The mixture was heated to reflux temperature (67-69°C) at a rate not exceeding 10°C/hour and stirred at reflux for about 1.5 hours. The reaction solution was cooled, 800 L of methanol was added and stirred at 3 to 10 °C for about 1 hour. The precipitated crystals were separated, washed with methanol and dried to give 407 kg of methyl 2-[[(2'-cyanobiphenyl-4-yl)methyl]amino]-3-nitrobenzoate [MBN] in 75% yield (based on MPB). Melting point: 140 to 141 °C. 1H-NMR (200 MHz, DMSO-d6) δ: 3.84 (3H, s), 4.26 (2H, m), 6.86 (1H, t), 7.46 (2H, d), 7.54-7.65 (4H, m), 7.79 (1H, d), 7.95 (1H, dd), 8.05-8.11 ( 2H, m), 8.67 (1H, t).

References