Water → (+/-)-(4R*,5R*)-5-((1S*)-methoxy-2-thienylmethyl)-l-methyl-4-phenylpyrrolidin-2-one

HRID 1837999Notes

Reaction equation

HRID 1837999 reaction equation
[H-].[Na+].[OH:3][C@H:4]([C:18]1[S:19][CH:20]=[CH:21][CH:22]=1)[C@@H:5]1[N:9]([CH3:10])[C:8](=[O:11])[CH2:7][C@@H:6]1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[CH3:23]I.O>CN(C=O)C>[CH3:23][O:3][C@H:4]([C:18]1[S:19][CH:20]=[CH:21][CH:22]=1)[C@@H:5]1[N:9]([CH3:10])[C:8](=[O:11])[CH2:7][C@@H:6]1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 14071421(+/-)-(4R*,5R*)-5-((1S *)-Hydroxy-2-thienylmethyl)-1-methyl4-phenyl-pyrrolidin-2-one

Product 1

HCID 59066526(+/-)-(4R*,5R*)-5-((1S*)-methoxy-2-thienylmethyl)-l-methyl-4-phenylpyrrolidin-2-oneYield 46.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a slurry of NaH (60%, 32 mg, 1.0 mmol) in DMF (15 mL) was added (±)-(4R*,5R*)-5-((1S)-hydroxy-2-thienylmethyl)-1-methyl-4-phenylpyrrolidin-2-one (Example 5 step 1, 250 mg, 0.9 mmol). The resulting mixture was stirred for 30 min, then methyl iodide (0.08 mL, 1.3 mmol) was added. After 2 h water was added and the resulting mixture was extracted with EtOAc, dried (MgSO4) and concentrated under reduced pressure. The residue was purified by flash chromatography (EtOAc) to give (±)-(4R*,5R*)-5-((1S*)-methoxy-2-thienylmethyl)-1-methyl-4-phenylpyrrolidin-2-one (125 mg, 46%) as a white solid: mp 101-102° C.; TLC (EtOAc/hex) Rf 0.50.

Workup

  1. extractionthe resulting mixture was extracted with EtOAc
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by flash chromatography (EtOAc)

Sources & evidence

ORD record
ord-9272b24899d24fc7802855b6ad6ca6ee
Source dataset
uspto-grants-2004_08
Patent number
US06784167B2

Reaction notes

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