Acetic Acid → 4-Bromo-2-{(1S,2S)-1-[1-(4-methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridine
Reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8](=O)[CH2:9][CH2:10][CH:11]=O)[CH:3]=1.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[CH3:32][O:33][C:34]1[CH:39]=[CH:38][C:37]([C@H:40]([NH2:42])[CH3:41])=[CH:36][CH:35]=1>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C@@H:8]2[CH2:9][CH2:10][CH2:11][N:42]2[C@H:40]([C:37]2[CH:38]=[CH:39][C:34]([O:33][CH3:32])=[CH:35][CH:36]=2)[CH3:41])[CH:3]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -70 °C
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.
Workup
- temperaturewarmed up to room temperature
- customby removing the ice bath
- stirringstir for another 2 hours
- customThe reaction mixture is quenched
- additionby adding water (25 mL)
- washis washed with 4×20 mL of water
- concentrationThe combined organic layers is concentrated
- custompurified by flash column chromatography (hexane 70%, EtOAc 30%)
Sources & evidence
- ORD record
- ord-f62b1571504145b390a3afcb79832e31
- Source dataset
- uspto-grants-2013_10
- Patent number
- US08546336B2
Reaction notes
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