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

HRID 409466Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 409466
[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]

Komponenten

8

Edukt 3

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

Produkt 1

HCID 59614354(2S,3S,5R)-2-benzyl-3-benzylamino-5-ethyl-pyrrolidine-1-carboxylic acid isopropyl esterAusbeute 55,3 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 11026Titanium isopropoxideKatalysatorHCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 14798Sodium HydroxideLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-13b6a57c964d4eecaaa4021f11b4d010
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08759365B2

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