Ammonium Chloride → rac-(S*)-5-(2,6-dimethoxyphenyl)-3-methylene-1-(4-(trifluoromethoxy)benzyl)pyrrolidin-2-one

HRID 594403Notes

Reaction equation

HRID 594403 reaction equation
[Li][CH2:2]CCC.[CH3:6][O:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([O:14][CH3:15])[C:9]=1[CH:16]1[N:20]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=2)[C:19](=[O:33])[C:18](=O)[CH2:17]1.[NH4+].[Cl-]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[CH3:6][O:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([O:14][CH3:15])[C:9]=1[CH:16]1[N:20]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][C:29]([F:30])([F:32])[F:31])=[CH:24][CH:23]=2)[C:19](=[O:33])[C:18](=[CH2:2])[CH2:17]1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 690846265-(2,6-Dimethoxyphenyl)-1-(4-(trifluoromethoxy)benzyl)pyrrolidine-2,3-dioneHCID 178418339Butyllithium

Product 1

HCID 86695633rac-(S*)-5-(2,6-dimethoxyphenyl)-3-methylene-1-(4-(trifluoromethoxy)benzyl)pyrrolidin-2-one

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A cooled (−78° C.) mixture of methyltriphenylphosphonium bromide (754 mg; 2.11 mmol) in anh. THF (6 ml) was treated dropwise with a solution of n-BuLi (1.6 M in hexanes; 1.32 ml; 2.11 mmol). Stirring was then continued at rt, under nitrogen, for 30 min. The resulting mixture was then cooled to 0° C., and treated with a solution of 5-(2,6-dimethoxyphenyl)-1-(4-(trifluoromethoxy)-benzyl)pyrrolidine-2,3-dione (800 mg; 1.95 mmol) in anh. THF (4 ml). Stirring was continued at 0° C. for 25 min., and at 60° C. for 1 h. After cooling to rt, aq. sat. NH4Cl (25 ml) was added, and this mixture was extracted with AcOEt (3×50 ml). 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-(S*)-5-(2,6-dimethoxyphenyl)-3-methylene-1-(4-(trifluoromethoxy)benzyl)pyrrolidin-2-one as a colorless oil. LC-MS (conditions A): tR=0.93 min.; [M+H]+: 408.29 g/mol.

Workup

  1. temperatureA cooled
  2. stirringStirring
  3. waitwas continued at 0° C. for 25 min.
  4. waitat 60° C. for 1 h
  5. temperatureAfter cooling to rt
  6. extractionthis mixture was extracted with AcOEt (3×50 ml)
  7. dry with materialThe mixed organic layers were dried over anh. MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to dryness under reduced pressure
  10. customPurification by FC (DCM/MeOH=30/1)

Sources & evidence

ORD record
ord-8b38badd18fb4bab95412ba068111d6f
Source dataset
uspto-grants-2016_01
Patent number
US09242970B2

Reaction notes

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