3-Chlorophenol → (+/-)-(4R* 5R*)-5-[(3-chlorophenoxy)methyl]-1-methyl-4-phenylpyrrolidin-2-one

HRID 1837986Notes

Reaction equation

HRID 1837986 reaction equation
[OH:1][CH2:2][C@@H:3]1[N:7]([CH3:8])[C:6](=[O:9])[CH2:5][C@@H:4]1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl:35][C:36]1[CH:37]=[C:38](O)[CH:39]=[CH:40][CH:41]=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[Cl:35][C:36]1[CH:41]=[C:40]([CH:39]=[CH:38][CH:37]=1)[O:1][CH2:2][C@@H:3]1[N:7]([CH3:8])[C:6](=[O:9])[CH2:5][C@@H:4]1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

6

Reactant 4

HCID 79333-ChlorophenolHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 13825981(4R,5R)-5-(hydroxymethyl)-1-methyl-4-phenylpyrrolidin-2-one2×

Product 1

HCID 69891684(+/-)-(4R* 5R*)-5-[(3-chlorophenoxy)methyl]-1-methyl-4-phenylpyrrolidin-2-oneYield 23%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (±)-(4R*,5R*)-5-(hydroxymethyl)-1-methyl-4-phenylpyrrolidin-2-one (Intermediate T prepared by Method 2, 220 mg, 1.1 mmol), PPh3 (422 mg, 1.6 mmol) and 3-chlorophenol (0.13 mL, 1.6 mmol) in THF (10 mL) was added DIAD (0.31 mL, 1.6 mmol). The reaction mixture was stirred overnight, then concentrated under reduced pressure and purified by flash chromatography (30% EtOAc/CH2Cl2) to afford (±)-(4R*,5R*)-5-[(3-chlorophenoxy)methyl]-1-methyl-4-phenylpyrrolidin-2-one (80 mg, 23%) as a colorless oil. TLC (75% EtoAc/25% hexanes) Rf 0.29, CI m/z (rel abundance) 316 ([MH]+, 100%).

Workup

  1. concentrationconcentrated under reduced pressure
  2. custompurified by flash chromatography (30% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-f89e49e805104be582a852189774e00c
Source dataset
uspto-grants-2004_08
Patent number
US06784167B2

Reaction notes

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