反応 #58591

反応方程式

2-chloroacrylonitrile

N-benzyl ethanolamine

potassium tert-butoxide

THF

→

4-Benzyl-morpholine-2-carboxylic acid hydrochloride

収率 61.0%

溶媒

toluene

toluene

反応条件

後処理

1. 1
   温度cooled to −5° C.
2. 2
   温度maintaining the temperature at −5° C. to 0° C
3. 3
   workup.STIRRINGThe mixture is post-agitated at about −5° C. to 0° C. for 1 h
4. 4
   その他quenched
5. 5
   workup.ADDITIONby adding water (45.9 mL)
6. 6
   その他The aqueous layer is separated
7. 7
   洗浄the toluene layer is washed with water (45.9 mL)
8. 8
   温度to warm to room temperature
9. 9
   濃縮The organic layer is then concentrated under reduced pressure at 40° C
10. 10
    workup.ADDITIONThen, the mixture is diluted with toluene (100 mL)
11. 11
    抽出extracted with 6N HClaq (162 mL)
12. 12
    温度This aqueous layer is heated up to the
13. 13
    温度reflux for 1 h 30
14. 14
    workup.STIRRINGto stir at room temperature overnight
15. 15
    その他After crystallization of 91
16. 16
    ろ過the solid is filtered
17. 17
    洗浄rinsed with 6N HClaq (40 mL)
18. 18
    その他dried
19. 19
    その他at 40° C.

実験手順

A 500 mL reactor under N2 is successively loaded with toluene (36.72 mL) and 2-chloroacrylonitrile (10.7 g, 122.23 mmol) at room temperature. Then, N-benzyl ethanolamine (18.36 g, 121.14 mmol) is added over 5 min and the reaction mixture is post-agitated at room temperature for 16 h. Then, the mixture is diluted with toluene (110.16 mL), cooled to −5° C. and 2M potassium tert-butoxide solution in THF (121.14 mmol) is slowly added over 30 min, maintaining the temperature at −5° C. to 0° C. The mixture is post-agitated at about −5° C. to 0° C. for 1 h, then quenched by adding water (45.9 mL). The aqueous layer is separated and the toluene layer is washed with water (45.9 mL) and then the mixture is allowed to warm to room temperature. The organic layer is then concentrated under reduced pressure at 40° C. Then, the mixture is diluted with toluene (100 mL) and extracted with 6N HClaq (162 mL). This aqueous layer is heated up to the reflux for 1 h 30, then the mixture is allowed to stir at room temperature overnight. After crystallization of 91, the solid is filtered, rinsed with 6N HClaq (40 mL) and dried under reduce pressure at 40° C. (19 g, yield=61%).

出典