反应详情

温度

-30 °C

Triphosgene (38.87 g, 0.1276 mol, 0.9 eq) and Compound 9 (51.14 g, 0.1412 mo, 1 eq.) were charged to a reactor. Anhydrous THF (486 mL, 9.5 vol) was then added and the clear solution was cooled to −30±5° C. Diisopropylethylamine (73.79 mL, 0.424 mol, 3.0 eq) in THF (103 mL, 2.5 vol) was charged to the reactor keeping the temperature below −20° C. After addition, the reaction mixture was warmed to 20±3° C. The mixture was stirred for 2 hours and was then filtered through Celite®, and the cake was rinsed with THF (767 mL, 15 vol). The filtrate was cooled to −30° C. and anhydrous NH3 (3 equiv.) added. The resulting white slurry was purged with N2 and warmed up to 20±3° C. for 1 hour. The reaction mixture was then cooled to 0±5° C. for 30 minutes. The mixture was again filtered and the reactor was rinsed with THF (255 mL, 5 vol). The cake was rinsed with H2O (255 mL, 5.0 vol) followed by 1N H2SO4 (10 vol). The solid was then transferred to a vacuum oven and dried at 35±3° C. to give the title Compound, 10, as a white solid. (1H NMR, 500 MHz; DMSO-d6) δ 7.97 (d, 1H), 7.85 (s, 1H), 7.56 (quin, 1H), 7.45 (q, 1H), 7.40 (s, 2H), 7.28 (t, 3H), 7.15 (td, 1H), 7.06 (d, 1H).

1. customthe temperature below −20° C
2. additionAfter addition
3. temperaturethe reaction mixture was warmed to 20±3° C
4. filtrationwas then filtered through Celite®
5. washthe cake was rinsed with THF (767 mL, 15 vol)
6. temperatureThe filtrate was cooled to −30° C.
7. customThe resulting white slurry was purged with N2
8. temperaturewarmed up to 20±3° C. for 1 hour
9. temperatureThe reaction mixture was then cooled to 0±5° C. for 30 minutes
10. filtrationThe mixture was again filtered
11. washthe reactor was rinsed with THF (255 mL, 5 vol)
12. washThe cake was rinsed with H2O (255 mL, 5.0 vol)
13. customdried at 35±3° C.