反应详情

温度

60 °C

A mixture of 2c (50 g, 1.00 equivalent), 5% Pd/C (0.75 g, 50% water, 0.75 wt %) and isopropyl acetate (400 ml, 8 volumes) was added to a hydrogenation vessel under nitrogen and heated to 60° C. The vessel was pressurized with hydrogen (1.00 bar overpressure) and the mixture stirred at 60° C. The reaction was complete within 3 hours. The pressure was released and the vessel purged with nitrogen. The mixture was filtered through a pad of Celite® and then the hydrogenation vessel and pad were rinsed with isopropyl acetate (100 ml, 2 volumes). The solution of 2d in isopropyl acetate was then combined with a solution of sodium sulfate (29.3 g, 1.10 equivalents) in water (150 ml, 3 vol) and then the mixture was heated to 70° C. Phenyl chloroformate (25.7 ml, 1.10 equivalents) was then added to the mixture while maintaining a temp. of 70° C. The reaction was stirred for 30 min after the end of addition and then the stirring was stopped. The phases were allowed to separate and the aqueous phase was removed. Water (150 ml, 3 vol) was then added and the mixture stirred for an additional 30 min before the stirring was stopped. The phases were allowed to separate and the aqueous phase removed. The mixture was then distilled at atmospheric pressure to azeotropically remove water from the organic phase. Compound 2e precipitated from solution when all of the water was removed. Distillation continued until there were 4 volumes of solvent remaining. The mixture was cooled to 20° C. over 5 hours then filtered to isolate the solid. The reactor and filter cake were washed with isopropyl acetate (2 vol) then the cake was dried under vacuum at 50° C. to afford 61.1 g (91%) of 2e.

1. additionwas added to a hydrogenation vessel under nitrogen
2. customthe vessel purged with nitrogen
3. filtrationThe mixture was filtered through a pad of Celite®
4. washthe hydrogenation vessel and pad were rinsed with isopropyl acetate (100 ml, 2 volumes)
5. temperaturethe mixture was heated to 70° C
6. temperaturewhile maintaining a temp
7. customof 70° C
8. stirringThe reaction was stirred for 30 min
9. additionafter the end of addition
10. customto separate
11. customthe aqueous phase was removed
12. additionWater (150 ml, 3 vol) was then added
13. stirringthe mixture stirred for an additional 30 min before the stirring
14. customto separate
15. customthe aqueous phase removed
16. distillationThe mixture was then distilled at atmospheric pressure to azeotropically remove water from the organic phase
17. customCompound 2e precipitated from solution when all of the water
18. customwas removed
19. distillationDistillation
20. temperatureThe mixture was cooled to 20° C. over 5 hours
21. filtrationthen filtered
22. customto isolate the solid
23. filtrationThe reactor and filter cake
24. washwere washed with isopropyl acetate (2 vol)
25. customthe cake was dried under vacuum at 50° C.