Benzylamine → (2S,3S,5R)-2-benzyl-3-benzylamino-5-ethyl-pyrrolidine-1-carboxylic acid isopropyl ester

HRID 409466ノート

反応式

HRID 409466 の反応式
[CH:1]([O:4][C:5]([N:7]1[CH:11]([CH2:12][CH3:13])[CH2:10][C:9](=O)[C@@H:8]1[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:6])([CH3:3])[CH3:2].[CH2:22]([NH2:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[BH4-].[Na+]>CO.O.[OH-].[Na+].CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH:1]([O:4][C:5]([N:7]1[C@H:11]([CH2:12][CH3:13])[CH2:10][C@H:9]([NH:29][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C@@H:8]1[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:6])([CH3:3])[CH3:2]

参加物

8

反応物 3

HCID 7504BenzylamineHCID 4311764Sodium borohydrideHCID 59614420(2S)-2-benzyl-5-ethyl-3-oxo-pyrrolidine-1-carboxylic acid isopropyl ester

生成物 1

HCID 59614354(2S,3S,5R)-2-benzyl-3-benzylamino-5-ethyl-pyrrolidine-1-carboxylic acid isopropyl ester収率 55.3%

試薬・触媒・溶媒 4

HCID 11026Titanium isopropoxide触媒HCID 887Methanol溶媒HCID 962Water溶媒HCID 14798Sodium Hydroxide溶媒

実験手順

To a solution of a diastereomeric mixture of (2S)-2-benzyl-5-ethyl-3-oxo-pyrrolidine-1-carboxylic acid isopropyl ester (0.29 mmol; 84 mg) and benzylamine (0.58 mmol; 62.1 mg) in MeOH (1.5 mL) is added titanium(IV) isopropoxide (0.58 mmol; 165 mg) at room temperature under nitrogen. After stirring for 5 hours, NaBH4 (0.58 mmol; 22 mg) is added to the mixture at 0° C. The mixture is stirred for 2 hours at room temperature and then diluted with water and aqueous 0.1 M NaOH solution. The solution is filtered and concentrated under reduced pressure. To the residue is added water and dichloromethane. The product is extracted twice with dichloromethane. The combined organic layer is washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel (n-hexane/EtOAc) to give (2S,3S,5R)-2-benzyl-3-benzylamino-5-ethyl-pyrrolidine-1-carboxylic acid isopropyl ester (61 mg, 55%); ESI-MS m/z: 381 [M++1], Retention time 1.77 min (condition A).

後処理

  1. stirringThe mixture is stirred for 2 hours at room temperature
  2. filtrationThe solution is filtered
  3. concentrationconcentrated under reduced pressure
  4. additionTo the residue is added water and dichloromethane
  5. extractionThe product is extracted twice with dichloromethane
  6. washThe combined organic layer is washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue is purified by column chromatography on silica gel (n-hexane/EtOAc)

出典と根拠

ORDレコード
ord-13b6a57c964d4eecaaa4021f11b4d010
出典データセット
uspto-grants-2014_06
特許番号
US08759365B2

反応ノート

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