反应详情

温度

10 °C

To a solution of 2-[bis(tert-butoxycarbonyl)amino]-5-bromopyrimidine 10 (216 kg crude, 460 mol, assuming quantitative yield in previous step) in anhydrous ethanol (1692 L) was slowly added a solution of sodium hydroxide (55.2 kg, 1380 mol) in water (344 L) while maintaining the temperature at 0-20° C. The mixture was stirred at that temperature until the content of 2-[bis(tert-butoxycarbonyl)-amino]-5-bromopyrimidine (10) was ≦0.5% by HPLC. The reaction mixture was cooled to 0-5° C. and the pH was adjusted to 7 by addition of oxalic acid (86.0 kg, 955 mol) while maintaining the temperature below 5° C. The mixture was then distilled under vacuum to a volume of 500-600 L while controlling the temperature below 50° C. Water (800 kg) was added and the mixture was stirred for 1 h. The solid was collected by filtration and stirred with water (2×500 L). The resulting solid was collected by filtration and dried under reduced pressure at 50° C. to afford tert-butyl 5-bromopyrimidin-2-ylcarbamate 11 (107 kg, 85% yield over two steps). 1H NMR (500 MHz, CDCl3) δ 8.63 (s, 2H), 8.12 (s, 1H), 1.55 (s, 9H). LCMS (ESI) m/z [M+H-Boc] 176

1. temperatureThe reaction mixture was cooled to 0-5° C.
2. temperaturewhile maintaining the temperature below 5° C
3. distillationThe mixture was then distilled under vacuum to a volume of 500-600 L
4. customthe temperature below 50° C
5. additionWater (800 kg) was added
6. filtrationThe solid was collected by filtration
7. stirringstirred with water (2×500 L)
8. filtrationThe resulting solid was collected by filtration
9. customdried under reduced pressure at 50° C.