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

HRID 1922165노트

반응식

HRID 1922165 반응식
[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]

참가 물질

4

반응물 2

HCID 4311764Sodium borohydride2회HCID 57347267(S)-tert-butyl 3-(3-methylbutanoyl)pyrrolidine-1-carboxylate

생성물 1

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

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-5d5f54b33a924a45b3b23e55b91edf3e
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08173821B2

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