反应 #1121788

反应方程式

butyl lithium

3-bromo-5-{(S)-1-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridine

3-Bromo-5-{(S)-1-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridine

4-fluoro-N-methoxy-N-methyl-benzamide

4-Fluoro-N-methoxy-N-methyl-benzamide

→

(4-fluoro-phenyl)-(5-{(S)-1-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-3-yl)-methanone

收率 95.3%

(4-Fluoro-phenyl)-(5-{(S)-1-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-3-yl)-methanone

收率 95.3%

溶剂

ether

ether

反应条件

后处理

1. 1
   温度(maintaining internal T<−70° C.)
2. 2
   workup.STIRRINGAfter stirring at −70° C. for 1.5 hours
3. 3
   其他the reaction is quenched by addition of 20 mL of water
4. 4
   温度warmed to room temperature
5. 5
   workup.STIRRINGwith stirring
6. 6
   workup.ADDITIONThe resulting mixture is diluted with 100 mL of EtOAc
7. 7
   洗涤washed with 2×30 mL of water
8. 8
   浓缩The organic layer is concentrated
9. 9
   其他purified by flash column chromatography (CH2Cl2 95%, EtOAc 5%)

实验过程

To a solution of 3-bromo-5-{(S)-1-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridine (3) (6.0 g, 16.6 mmole) in 100 mL of ether at −73° C., is added a solution of butyl lithium (7.3 mL, 18.3 mmole, 2.5 M in hexane) slowly (maintaining internal T<−70° C.). After stirring at −73° C. for 30 minutes, a solution of 4-fluoro-N-methoxy-N-methyl-benzamide (4a) (4.56 g, 24.9 mmole) in 15 mL of ether is added slowly (maintaining internal T<−70° C.). After stirring at −70° C. for 1.5 hours, the reaction is quenched by addition of 20 mL of water and warmed to room temperature with stirring. The resulting mixture is diluted with 100 mL of EtOAc and washed with 2×30 mL of water. The organic layer is concentrated and purified by flash column chromatography (CH2Cl2 95%, EtOAc 5%) to give (4-fluoro-phenyl)-(5-{(S)-1-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-3-yl)-methanone (4) (6.4 g, yield 86%) as a light brown viscose liquid.

来源