Water → 3-Methyl-2-oxo-1-phenylpyrrolidine-3-carboxylic acid

HRID 418697Notes

Reaction equation

HRID 418697 reaction equation
[C:1]1([N:7]2[CH2:11][CH2:10][CH:9]([C:12]([OH:14])=[O:13])[C:8]2=[O:15])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li+].[CH3:17]C([N-]C(C)C)C.IC.O>O1CCCC1.C(OCC)(=O)C>[CH3:17][C:9]1([C:12]([OH:14])=[O:13])[CH2:10][CH2:11][N:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:8]1=[O:15]

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 30437622-Oxo-1-phenylpyrrolidine-3-carboxylic acid

Product 1

HCID 587902463-Methyl-2-oxo-1-phenylpyrrolidine-3-carboxylic acidYield 80%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 1-phenyl-2-oxo-3-pyrrolidinecarboxylic acid (205) (200 mg, 0.975 mmol) in dry tetrahydrofuran (5 mL) at −78° C. was added LDA (1.5M solution in cyclohexane, 1.63 mL, 2.44 mmol) and the mixture was stirred for 40 min. Iodomethane (152 μL, 2.44 mmol) was added and the reaction mixture was allowed to warm to room temperature and stirring was continued for 16 h. Water and ethyl acetate were added. The aqueous layer was collected, acidified to pH 4 with a 1N HCl solution and extracted twice with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent methanol-dichloromethane 2:98) to afford title compound 313 (170 mg, 80% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 7.67 (dd, J=8.8, 1.2 Hz, 2H), 7.39 (dd, J=8.8, 7.2 Hz, 2H), 7.16 (tt, J=7.2, 1.2 Hz, 1H), 3.92-3.80 (m, 2H), 2.54-2.46 (m, 1H), 2.08-1.98 (m, 1H), 1.34 (s, 3H).

Workup

  1. stirringstirring
  2. waitwas continued for 16 h
  3. customThe aqueous layer was collected
  4. extractionextracted twice with ethyl acetate
  5. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  6. customthe solvent was removed under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel (eluent methanol-dichloromethane 2:98)

Sources & evidence

ORD record
ord-8a66261b5a1744f598ae5bc9aa7bcc20
Source dataset
uspto-grants-2012_01
Patent number
US08093264B2

Reaction notes

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