tert-Butanol → Methyl 2-((tert-butoxycarbonyl)amino)-3-nitrobenzoate

Participants

Reaction Conditions

Reaction Steps

In dimethylformamide [DMF] (242 kg) was dissolved methyl 2-carboxy-3-nitrobenzoate [MNA] (164 kg) obtained in Reference Example 1. To the solution was dropped diphenylphosphorylazide [DPPA] (204 kg) at room temperature and then triethylamine (87 kg) at the temperature ranging 20-35° C. After the solution was stirred at 20-30° C. for about 3 hours, t-butylalcohol (930 kg) was added to the reaction solution. The solution was heated for 3-5 hours to 85-90° C. and then stirred for 1-2 hours under reflux (85-90° C.). The reaction solution was cooled, concentrated and dissolved in ethyl acetate(1400 L). The solution was washed with a mixture of 15% hydrochloric acid (160 L) and water (1890 L), water (660 L), 5% solution of sodium bicarbonate (1100 kg), and water (660 L), in this order and the organic layer was concentrated under reduced pressure. To the concentrate was added methanol (300 kg) and then were added crystal seeds (15 kg) and methanol (450 kg). The solution was heated to 50-60° C. to dissolve insoluble materials. The solution was cooled to 5° C. and precipitated crystals were separated. The crystals were washed with cooled methanol (100 L) and dried to give methyl 2-t-butoxycarbonylamino-3-nitrobenzoate [BAN] (187.0 kg, 86.7%). Mother liquor and the methanol solution used for washing the crystals was concentrated under reduced pressure and cooled. The precipitated crystals were centrifuged, washed with cooled methanol and dried to obtain the second crystals of BAN.

Provenance & Evidence