Réaction #1121788

Équation de réaction

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

Rendement 95.3%

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

Rendement 95.3%

Solvants

ether

ether

Conditions de réaction

Traitement

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

Mode opératoire

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.

Source