反应详情

A 6 L Parr bottle is loaded with 51b (1021 g), i-propanol (3630 mL) and water (639 mL). After purging with N2, 5% Pd—C 52% wet is added (105.6 g) and the mixture is then pressurized with hydrogen (50 psi). The reaction mixture is shaken for 9 h 30 mins, then the mixture is filtered on a Hyflo Super Cel® pad (100 g) pre-imbibed with 80/20 i-propanol/water (500 mL). The catalyst is rinsed with a 80:20: i-propanol:water mixture (500 mL). The solvents are stripped off then i-propanol is added (2000 mL) to be partially removed again. Then i-propanol is re-added (1400 mL) and the heterogeneous mixture is concentrated to provide an off-white solid To this crude alcohol 52b is added i-propanol (4474 mL) and the mixture is heated to reflux until a homogeneous solution is formed. Then, the mixture is cooled slowly and the crystallization starts at 60° C. The powder is filtered at room temperature, rinsed with i-propanol (2×350 mL) and dried under reduced pressure at 40° C. to give highly pure compound 52b with 80% recovery yield (98.4% de, 99.2% ee).

1. customAfter purging with N2, 5% Pd—C 52%
2. additionwet is added (105.6 g)
3. filtrationthe mixture is filtered on a Hyflo Super Cel® pad (100 g) pre-imbibed with 80/20 i-propanol/water (500 mL)
4. washThe catalyst is rinsed with a 80:20
5. additioni-propanol is added (2000 mL)
6. customto be partially removed again
7. additionThen i-propanol is re-added (1400 mL)
8. concentrationthe heterogeneous mixture is concentrated
9. customto provide an off-white solid To this crude alcohol 52b
10. temperaturethe mixture is heated
11. temperatureto reflux until a homogeneous solution
12. customis formed
13. temperatureThen, the mixture is cooled slowly
14. customthe crystallization
15. customstarts at 60° C
16. filtrationThe powder is filtered at room temperature
17. washrinsed with i-propanol (2×350 mL)
18. customdried under reduced pressure at 40° C.