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

HRID 409466Notes

Reaction equation

HRID 409466 reaction equation
[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]

Participants

8

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 4

HCID 11026Titanium isopropoxideCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 14798Sodium HydroxideSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-13b6a57c964d4eecaaa4021f11b4d010
Source dataset
uspto-grants-2014_06
Patent number
US08759365B2

Reaction notes

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