Reaction #1121798

Reaction equation

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

(4-fluoro-phenyl)-methyl-amine

2-(dicyclohexylphosphino)-biphenyl

potassium tert-butoxide

→

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

Yield 95.0%

Solvents

EtOAc

Water

toluene

Conditions

Workup

1. 1
   Temperaturecooled to room temperature
2. 2
   OtherThe layers are separated
3. 3
   Extractionthe aqueous layer is extracted with EtOAc
4. 4
   WashThe combined organic layers are washed with brine
5. 5
   Dryingdried over Na2SO4
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated down
8. 8
   OtherThe crude product is purified by chromatography (EtOAc/hexane: 10%˜40%)

Procedure

To a solution of 1-(2-chloro-5-fluoro-4-{(S)-1-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridine (100 mg, 0.30 mmol) in toluene (25 mL) are added (4-fluoro-phenyl)-methyl-amine (48 mg, 0.39 mmol), 2-(dicyclohexylphosphino)-biphenyl (10 mg, 0.03 mmol), Pd2(dba)3 (14 mg, 0.015 mmol) and potassium tert-butoxide (84 mg, 0.75 mmol). The reaction mixture is stirred at 85° C. for 3 hours and cooled to room temperature. Water and EtOAc are added to the mixture. The layers are separated and the aqueous layer is extracted with EtOAc. The combined organic layers are washed with brine, dried over Na2SO4, filtered and concentrated down. The crude product is purified by chromatography (EtOAc/hexane: 10%˜40%) to give (5-fluoro-4-{(S)-[(R)-1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-2-yl)-(4-fluoro-phenyl)-methyl-amine (120 mg, 95%). M/Z=424.23 [M+1]

Source