Lithium borohydride → [(3RS,4SR)-3-(3,4-dichloro-phenyl)-4-((RS)-1-hydroxy-ethyl)-pyrrolidin-1-yl]-(6-methoxy-pyridin-3-yl)-methanone

HRID 906910Notes

Reaction equation

HRID 906910 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:13][N:12]([C:14]([C:16]3[CH:17]=[N:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=3)=[O:15])[CH2:11][CH:10]2[C:24](=[O:26])[CH3:25])[CH:5]=[CH:6][C:7]=1[Cl:8].[Li+].[BH4-]>CO>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH:10]([CH:24]([OH:26])[CH3:25])[CH2:11][N:12]([C:14]([C:16]3[CH:17]=[N:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=3)=[O:15])[CH2:13]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 671314081-[(3SR,4RS)-4-(3,4-Dichloro-phenyl)-1-(6-methoxy-pyridine-3-carbonyl)-pyrrolidin-3-yl]-ethanone

Product 1

HCID 67130175[(3RS,4SR)-3-(3,4-dichloro-phenyl)-4-((RS)-1-hydroxy-ethyl)-pyrrolidin-1-yl]-(6-methoxy-pyridin-3-yl)-methanoneYield 23.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of 1-[(3SR,4RS)-4-(3,4-dichloro-phenyl)-1-(6-methoxy-pyridine-3-carbonyl)-pyrrolidin-3-yl]-ethanone (XIV-1) (0.64 g, 1.60 mmol) in MeOH (10 mL) at −78° C. was added LiBH4 (0.047 g, 1.70 mmol). The temperature was slowly raised to RT (over 1 hour), and the reaction mixture was quenched by addition of H2O. The product was extracted with EtOAc, the combined organic phases were dried over Na2SO4. The two diastereoisomers were separated by column chromatography (SiO2) to yield 0.15 g (23%) of [(3RS,4SR)-3-(3,4-dichloro-phenyl)-4-((RS)-1-hydroxy-ethyl)-pyrrolidin-1-yl]-(6-methoxy-pyridin-3-yl)-methanone (XV-A-1) as a white solid ES-MS m/e: 395.3 (M+H+) and 0.48 g (75%) of [(3RS,4SR)-3-(3,4-dichloro-phenyl)-4-((SR)-1-hydroxy-ethyl)-pyrrolidin-1-yl]-(6-methoxy-pyridin-3-yl)-methanone (XV-B-1) as a white solid ES-MS m/e: 395.3 (M+H+).

Workup

  1. customthe reaction mixture was quenched by addition of H2O
  2. extractionThe product was extracted with EtOAc
  3. dry with materialthe combined organic phases were dried over Na2SO4
  4. customThe two diastereoisomers were separated by column chromatography (SiO2)

Sources & evidence

ORD record
ord-a2b56f5b7cc54905bdda4f328386ceb1
Source dataset
uspto-grants-2011_09
Patent number
US08012998B2

Reaction notes

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