Methyl iodide → Methyl 1-(4-fluorophenyl)-3-methyl-2-oxopyrrolidine-3-carboxylate

HRID 1676320Notes

Reaction equation

HRID 1676320 reaction equation
[H-].[Li+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:14][CH2:13][CH:12]([C:15]([O:17][CH3:18])=[O:16])[C:11]2=[O:19])=[CH:6][CH:5]=1.IC.[CH3:22]COC(C)=O>CN(C=O)C>[F:3][C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH2:14][CH2:13][C:12]([CH3:22])([C:15]([O:17][CH3:18])=[O:16])[C:11]2=[O:19])=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 8857Ethyl AcetateHCID 62714Lithium hydrideHCID 67347273Methyl 1-(4-fluorophenyl)-2-oxopyrrolidine-3-carboxylate

Product 1

HCID 67348985Methyl 1-(4-fluorophenyl)-3-methyl-2-oxopyrrolidine-3-carboxylateYield 68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

LiH (13.8 mg, 1.737 mmol) was added to the solution of methyl 1-(4-fluorophenyl)-2-oxopyrrolidine-3-carboxylate (0.206 g, 0.868 mmol) in DMF (5 mL) at 0° C. After 30 minutes stirring, iodomethane (0.16 mL, 2.61 mmol) was added to the reaction mixture at 0° C., and then the reaction was warmed to room temperature. The reaction mixture was stirred for 17 hours and heated at 40° C. for 3 hours. After cooling to room temperature, the mixture was treated with EtOAc, quenched with ice water, extracted with EtOAc, washed with brine, dried over MgSO4, and concentrated to give the crude material that was purified by silica gel flash column chromatography (19:1=CH2Cl2:EtOAc) to afford 0.149 g (68%) of the desired product. LRMS (ESI pos) m/e 252.1 (M+1). 1H-NMR (400 MHz, CDCl3) δ 7.61 (m, 2H), 7.07 (m, 2H), 3.94 (m, 1H), 3.78 (m, 1H), 3.75 (s, 3H), 2.68 (m, 1H), 2.06 (m, 1H), 1.55 (s, 3H); 19F NMR (376 MHz, CDCl3) δ −117.6.

Workup

  1. stirringThe reaction mixture was stirred for 17 hours
  2. temperatureheated at 40° C. for 3 hours
  3. temperatureAfter cooling to room temperature
  4. customquenched with ice water
  5. extractionextracted with EtOAc
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customto give the crude material that
  10. customwas purified by silica gel flash column chromatography (19:1=CH2Cl2:EtOAc)

Sources & evidence

ORD record
ord-d60de9a919ff4b8ea44fbfa19b058617
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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