Reaction #1121795

Reaction equation

4-(4-bromo-pyridin-2-yl)-4-oxo-butyraldehyde

4-(4-Bromo-pyridin-2-yl)-4-oxo-butyraldehyde

acetic acid

NaBH(OAc)3

(R)-(+)-1-(4-methoxyphenyl)ethylamine

→

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

Yield 36.0%

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

Yield 36.0%

Solvents

CH2Cl2

Conditions

Workup

1. 1
   Temperaturewarmed up to room temperature
2. 2
   Otherby removing the ice bath
3. 3
   workup.STIRRINGstir for another 2 hours
4. 4
   OtherThe reaction mixture is quenched
5. 5
   workup.ADDITIONby adding water (25 mL)
6. 6
   Washis washed with 4×20 mL of water
7. 7
   ConcentrationThe combined organic layers is concentrated
8. 8
   Otherpurified by flash column chromatography (hexane 70%, EtOAc 30%)

Procedure

To a solution of 4-(4-bromo-pyridin-2-yl)-4-oxo-butyraldehyde (3) (720 mg, 2.97 mmol) in CH2Cl2 at −70° C. is added acetic acid (8.93 mg, 0.15 mmol), NaBH(OAc)3 (1.58 g, 7.44 mmol) and (R)-(+)-1-(4-methoxyphenyl)ethylamine (540 mg, 3.6 mmol). The reaction mixture is stirred at −70° C. for 1 hour, then warmed up to room temperature by removing the ice bath and letting it stir for another 2 hours. The reaction mixture is quenched by adding water (25 mL) is washed with 4×20 mL of water. The combined organic layers is concentrated and purified by flash column chromatography (hexane 70%, EtOAc 30%) to yield 4-bromo-2-{(1S,2S)-1-[1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridine (4) (386 mg, 36% yield) as a yellow solid: MS ES+363.10.

Source