Water → rac-(3S*,5S*)-5-(2,6-dimethoxyphenyl)-3-methoxy-1-(4-(trifluoromethoxy)benzyl)pyrrolidin-2-one

HRID 594400Notes

Reaction equation

HRID 594400 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[CH:11]1[N:15]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=2)[C:14](=[O:28])[CH:13]([OH:29])[CH2:12]1.[H-].[Na+].[CH3:32]I.O>C1COCC1.CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[CH:11]1[N:15]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]([F:25])([F:26])[F:27])=[CH:19][CH:18]=2)[C:14](=[O:28])[CH:13]([O:29][CH3:32])[CH2:12]1

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 69082591rac-(3S*,5S*)-5-(2,6-dimethoxyphenyl)-3-hydroxy-1-(4-(trifluoromethoxy)benzyl)pyrrolidin-2-one

Product 1

HCID 69081617rac-(3S*,5S*)-5-(2,6-dimethoxyphenyl)-3-methoxy-1-(4-(trifluoromethoxy)benzyl)pyrrolidin-2-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A cooled (0° C.) solution of rac-(3S*,5S*)-5-(2,6-dimethoxyphenyl)-3-hydroxy-1-(4-(trifluoromethoxy)benzyl)pyrrolidin-2-one (53 mg; 0.12 mmol) in anh. THF (3 ml) was treated with NaH (60% dispersion in mineral oil; 6 mg; 0.14 mmol). Stirring was continued at 0° C., under nitrogen, for 5 min., and then at rt for 20 min. The mixture was again cooled to 0° C., and a solution of CH3I (20 mg; 0.14 mmol) in anh. THF (1 ml) was added. The obtained mixture was further stirred at 0° C. for 5 min., and then at rt for 17 h. Water and AcOEt were added, and the separated aq. layer was further extracted with AcOEt. The mixed organic layers were dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=30/1) afforded rac-(3S*,5S*)-5-(2,6-dimethoxyphenyl)-3-methoxy-1-(4-(trifluoromethoxy)benzyl)pyrrolidin-2-one as a yellow oil. LC-MS (conditions A): tR=0.88 min.; [M+H]+: 426.19 g/mol.

Workup

  1. waitat rt for 20 min
  2. stirringThe obtained mixture was further stirred at 0° C. for 5 min.
  3. waitat rt for 17 h
  4. extractionthe separated aq. layer was further extracted with AcOEt
  5. dry with materialThe mixed organic layers were dried over anh. MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure
  8. customPurification by FC (DCM/MeOH=30/1)

Sources & evidence

ORD record
ord-1163e61755874947b0c535befc10ba80
Source dataset
uspto-grants-2016_01
Patent number
US09242970B2

Reaction notes

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