反応 #58605

反応方程式

51b

2-[5-Fluoro-2-(methyloxy)phenyl]-1-[4-(phenylmethyl)morpholin-2-yl]-1-tetrahydro-2H-pyran-4-ylethanol hydrochloride

water

→

compound 52b

2-[5-Fluoro-2-(methyloxy)phenyl]-1-morpholin-2-yl-1-tetrahydro-2H-pyran-4-ylethanol hydrochloride

溶媒

i-propanol

i-propanol

反応条件

後処理

1. 1
   その他After purging with N2, 5% Pd—C 52%
2. 2
   workup.ADDITIONwet is added (105.6 g)
3. 3
   ろ過the mixture is filtered on a Hyflo Super Cel® pad (100 g) pre-imbibed with 80/20 i-propanol/water (500 mL)
4. 4
   洗浄The catalyst is rinsed with a 80:20
5. 5
   workup.ADDITIONi-propanol is added (2000 mL)
6. 6
   その他to be partially removed again
7. 7
   workup.ADDITIONThen i-propanol is re-added (1400 mL)
8. 8
   濃縮the heterogeneous mixture is concentrated
9. 9
   その他to provide an off-white solid To this crude alcohol 52b
10. 10
    温度the mixture is heated
11. 11
    温度to reflux until a homogeneous solution
12. 12
    その他is formed
13. 13
    温度Then, the mixture is cooled slowly
14. 14
    その他the crystallization
15. 15
    その他starts at 60° C
16. 16
    ろ過The powder is filtered at room temperature
17. 17
    洗浄rinsed with i-propanol (2×350 mL)
18. 18
    その他dried under reduced pressure at 40° C.

実験手順

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).

出典