反应 #170293

反应方程式

2-fluoro-4-hydroxybenzonitrile

K2CO3

K2CO3

bromoamide

(2R)-3-bromo-N-[4-cyano-3-(trifluoromethyl)phenyl]-2-hydroxy-2-methylpropanamide

→

(S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyano-3-fluorophenoxy)-2-hydroxy-2-methylpropanamide

收率 23.0%

溶剂

H2O

2-propanol

acetone

反应条件

后处理

1. 1
   温度to reflux for 2 h
2. 2
   浓缩concentrated under reduced pressure
3. 3
   其他to give a solid
4. 4
   温度was heated
5. 5
   温度to reflux for 3 h
6. 6
   浓缩concentrated under reduced pressure
7. 7
   其他to give a solid
8. 8
   萃取extracted with EtOAc (2×100 mL)
9. 9
   洗涤The combined EtOAc extracts were washed with 10% NaOH (4×100 mL) and brine
10. 10
    干燥The organic layer was dried over MgSO4
11. 11
    浓缩concentrated under reduced pressure
12. 12
    其他to give an oil which
13. 13
    其他was crystallized from CH2Cl2/hexane

实验过程

A mixture of bromoamide ((2R)-3-bromo-N-[4-cyano-3-(trifluoromethyl)phenyl]-2-hydroxy-2-methylpropanamide, R-19 (2.0 g, 5.70 mmol), anhydrous K2CO3 (2.4 g, 17.1 mmol) in 50 mL of acetone was heated to reflux for 2 h and then concentrated under reduced pressure to give a solid. The resulting solid was treated with 2-fluoro-4-hydroxybenzonitrile (1.2 g, 8.5 mmol) and anhydrous K2CO3 (1.6 g, 11.4 mmol) in 50 mL of 2-propanol was heated to reflux for 3 h and then concentrated under reduced pressure to give a solid. The residue was treated with 100 mL of H2O and then extracted with EtOAc (2×100 mL). The combined EtOAc extracts were washed with 10% NaOH (4×100 mL) and brine, successively. The organic layer was dried over MgSO4 and then concentrated under reduced pressure to give an oil which was crystallized from CH2Cl2/hexane to give 0.5 g (23%) of (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-3-(4-cyano-3-fluorophenoxy)-2-hydroxy-2-methylpropanamide as a colorless solid.

来源