Benzoic acid, 2-[[(1,1-dimethylethoxy)carbonyl]amino]-3-nitro-methyl ester

21606-04-2

121-44-8

75-65-0

57113-90-3

Methyl 3-nitro-2-carboxybenzoate (164 kg) was used as a raw material and dissolved in dimethylformamide (DMF, 242 kg). Diphenylphosphoryl azide (DPPA, 204 kg) was added to the solution at room temperature, followed by the slow dropwise addition of triethylamine (87 kg) while controlling the reaction temperature between 20 and 35 °C. After the reaction mixture was stirred at 20 to 30 °C for about 3 hours, tert-butanol (930 kg) was added. Subsequently, the reaction temperature was raised to 85 to 90 °C over a period of 3 to 5 hours and stirred and refluxed at this temperature for 1 to 2 hours. Upon completion of the reaction, the reaction solution was cooled and concentrated. The concentrated residue was dissolved in ethyl acetate (1400 L) and washed sequentially with a mixture of 15% hydrochloric acid (160 L) and water (1890 L), water (660 L), 5% aqueous sodium bicarbonate (1100 kg), and water (660 L). The organic layer was concentrated under reduced pressure to give a crude product. The crude product was dissolved in methanol (300 kg), crystalline seed (15 kg) and additional methanol (450 kg) were added and heated to 50-60 °C to dissolve it completely. Subsequently cooled, the precipitated crystals were separated and washed with cold methanol (100 L) and dried to give methyl 2-((tert-butoxycarbonyl)amino)-3-nitrobenzoate (BAN, 187.0 kg, 86% yield). The mother liquor and washings were concentrated under reduced pressure and cooled, and the precipitated crystals were separated by centrifugation, washed with cold methanol and dried to give a second batch of BAN crystals. The product was analyzed by 1H-NMR (200 MHz, CDCl3) and IR (KBr) to confirm the structure.