Sodium borohydride → (3S)-3-(1-hydroxy-3-methyl-butyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1922165Notes

Reaction equation

HRID 1922165 reaction equation
[BH4-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:14][CH2:13][C@H:12]([C:15](=[O:20])[CH2:16][CH:17]([CH3:19])[CH3:18])[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]>CO>[C:3]([O:7][C:8]([N:10]1[CH2:14][CH2:13][C@H:12]([CH:15]([OH:20])[CH2:16][CH:17]([CH3:18])[CH3:19])[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]

Participants

4

Reactant 2

HCID 4311764Sodium borohydride2×HCID 57347267(S)-tert-butyl 3-(3-methylbutanoyl)pyrrolidine-1-carboxylate

Product 1

HCID 59536655(3S)-3-(1-hydroxy-3-methyl-butyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Add sodium borohydride (15.2 g, 423 mmol) to a solution of (S)-3-(3-methylbutanoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (21.6 g, 84.6 mmol) in methanol (500 mL) portion wise and stir at room temperature overnight. Add another equivalent of sodium borohydride (3.04 g, 84.6 mmol). Stir for another 2 hours, evaporate the methanol to half the volume, add brine and extract with EtOAc. Dry the combined organic phases (MgSO4), filter and concentrate under reduced pressure. Separate the diastereoisomers by super critical fluid chromatography (AD-H column) eluting with 10% MeOH/CO2 with 0.2% diethylmethylamine to provide (3S)-3-(1-hydroxy-3-methyl-butyl)-pyrrolidine-1-carboxylic acid tert-butyl ester, isomer 1 (S-1) as the first eluting isomer (8.2 g, 38%) and (3S)-3-(1-hydroxy-3-methyl-butyl)-pyrrolidine-1-carboxylic acid tert-butyl ester, isomer 2 (S-2) as the second eluting isomer (8.9 g, 41%).

Workup

  1. stirringStir for another 2 hours
  2. customevaporate the methanol to half the volume
  3. additionadd brine
  4. extractionextract with EtOAc
  5. dry with materialDry the combined organic phases (MgSO4)
  6. filtrationfilter
  7. concentrationconcentrate under reduced pressure
  8. customSeparate the diastereoisomers by super critical fluid chromatography (AD-H column)
  9. washeluting with 10% MeOH/CO2 with 0.2% diethylmethylamine

Sources & evidence

ORD record
ord-5d5f54b33a924a45b3b23e55b91edf3e
Source dataset
uspto-grants-2012_05
Patent number
US08173821B2

Reaction notes

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