反应详情

温度

30 °C

Isonipecotamide (15.4, 120 mmol, 2.0 eq.) and IPA (200 mL) were added to the solution of biphenyl-2-yl-carbamic acid 1-{2-[(4-formylbenzoyl)methylamino]ethyl}piperidin-4-yl ester from the previous step. Liquid (200 mL) was distilled off and additional IPA (400 mL) was added under reduced pressure at 60° C. Liquid (400 mL) was distilled off over a period of 1.5 hours and additional IPA (600 mL) was added. Liquid (100 mL) was distilled off and the remaining solution was cooled to 30° C. to yield a hazy white mixture, which was then added to Na2SO4 (18 g). The flask was rinsed with IPA (100 mL) and added to the solution. The resulting mixture was cooled to room temperature and AcOH (20 mL, 360 mmol, 6.0 eq.) was added. The mixture was cooled to 18° C. with an ice bath and NaHB(OAc)3 (38.2 g, 180 mmol, 3.0 eq.) was added over 5 minutes. The mixture was allowed to warm up to 25° C. and was maintained at that temperature for 2 hours. Solvent was removed under reduced pressure, and the remaining material was used directly in the next step.

1. distillationLiquid (200 mL) was distilled off
2. additionadditional IPA (400 mL) was added under reduced pressure at 60° C
3. distillationLiquid (400 mL) was distilled off over a period of 1.5 hours
4. additionadditional IPA (600 mL) was added
5. distillationLiquid (100 mL) was distilled off
6. customto yield a hazy white mixture, which
7. washThe flask was rinsed with IPA (100 mL)
8. additionadded to the solution
9. temperatureThe resulting mixture was cooled to room temperature
10. temperatureThe mixture was cooled to 18° C. with an ice bath
11. temperatureto warm up to 25° C.
12. temperaturewas maintained at that temperature for 2 hours
13. customSolvent was removed under reduced pressure