Reacción #1121788

Ecuación de reacción

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

Rendimiento 95.3%

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

Rendimiento 95.3%

Disolventes

ether

ether

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperatura(maintaining internal T<−70° C.)
2. 2
   workup.STIRRINGAfter stirring at −70° C. for 1.5 hours
3. 3
   Otrothe reaction is quenched by addition of 20 mL of water
4. 4
   Temperaturawarmed to room temperature
5. 5
   workup.STIRRINGwith stirring
6. 6
   workup.ADDITIONThe resulting mixture is diluted with 100 mL of EtOAc
7. 7
   Lavadowashed with 2×30 mL of water
8. 8
   ConcentraciónThe organic layer is concentrated
9. 9
   Otropurified by flash column chromatography (CH2Cl2 95%, EtOAc 5%)

Procedimiento

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.

Fuente