Methanol → Methyl 1-(2,4-dimethoxybenzyl)-5-oxopyrrolidine-3-carboxylate

HRID 58889Notes

Reaction equation

HRID 58889 reaction equation
O=S(Cl)Cl.[CH3:5][O:6][C:7]1[CH:22]=[C:21]([O:23][CH3:24])[CH:20]=[CH:19][C:8]=1[CH2:9][N:10]1[C:14](=[O:15])[CH2:13][CH:12]([C:16]([OH:18])=[O:17])[CH2:11]1.[CH3:25]O>>[CH3:5][O:6][C:7]1[CH:22]=[C:21]([O:23][CH3:24])[CH:20]=[CH:19][C:8]=1[CH2:9][N:10]1[C:14](=[O:15])[CH2:13][CH:12]([C:16]([O:18][CH3:25])=[O:17])[CH2:11]1

Participants

4

Reactant 3

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 112544611-(2,4-Dimethoxybenzyl)-5-oxopyrrolidine-3-carboxylic acid

Product 1

HCID 67439104Methyl 1-(2,4-dimethoxybenzyl)-5-oxopyrrolidine-3-carboxylateYield 81%

Procedure

SOCl2 (6.4 g, 54 mmol) was added dropwise to methanol (40 mL) followed by addition of 1-(2,4-dimethoxybenzyl)-5-oxopyrrolidine-3-carboxylic acid (5.0 g, 18 mmol) at 0° C. The reaction mixture was stirred at ambient temperature for 1 h and then heated under reflux for 7 h. The mixture was cooled to ambient temperature and concentrated. The residue was purified by flash column chromatography on silica gel (petroleum ether/EtOAc=6:1 to 2:1) to afford methyl 1-(2,4-dimethoxybenzyl)-5-oxopyrrolidine-3-carboxylate (a mixture of two enantiomers, 4.3 g, 81% yield) as a colorless oil. The two enantiomers were separated by chiral prep-HPLC.

Workup

  1. temperatureheated
  2. temperatureunder reflux for 7 h
  3. temperatureThe mixture was cooled to ambient temperature
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography on silica gel (petroleum ether/EtOAc=6:1 to 2:1)

Sources & evidence

ORD record
ord-d7d95137c8494587ab35fa3d70aaf3a4
Source dataset
uspto-grants-2016_09
Patent number
US09434761B2

Reaction notes

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