Sulfuric Acid → (S)-Methyl 1-benzyl-5-oxopyrrolidine-2-carboxylate

HRID 2050935Notes

Reaction equation

HRID 2050935 reaction equation
[O:1]=[C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C@H:5]([C:14]([OH:16])=[O:15])[CH2:4][CH2:3]1.OS(O)(=O)=O.[OH-].[Na+].[C:24](=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.CO>[CH3:24][O:15][C:14]([C@@H:5]1[CH2:4][CH2:3][C:2](=[O:1])[N:6]1[CH2:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:16]

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 10900113(S)-1-Benzyl-5-carboxy-2-pyrrolidinone

Product 1

HCID 10998904(S)-Methyl 1-benzyl-5-oxopyrrolidine-2-carboxylate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

Procedure

The crude (S)-5-oxo-1-(phenylmethyl)-2-pyrrolidinecarboxylic acid (160 g, 0.73 mol) was dissolved in 300 mL of toluene and 550 mL of methanol. To the solution was added 9 mL of conc H2SO4 and the solution was heated to reflux overnight. The solution was cooled in an ice bath and neutralized to pH 5 with 25% NaOH, followed by adding 50 mL of saturated sodium bicarbonate to bring the solution to pH 7. The methanol was removed on a rotary evaporator and the residue was diluted with 500 mL of water and extracted with methylene chloride. The combined extracts were washed with brine and dried over MgSO4. Evaporation of the solvent afforded 132 g of (S)-5-oxo-1-(phenylmethyl)-2-pyrrolidinecarboxylic acid methyl ester as an oil which was >95% pure by NMR. 1H NMR (CDCl3) δ 2.0-2.6 (m,4H,CH2 's), 3.68 (s,3 H,CH3), 3.95 (dd, 1 H,J=4,9 Hz, H-4), 4.02 and 5.03 (AB, 2 H,Jgem =16 Hz, CH2Ph), 7.2-7.4 (m, 5 H, arom).

Workup

  1. temperaturethe solution was heated
  2. temperatureto reflux overnight
  3. temperatureThe solution was cooled in an ice bath
  4. customThe methanol was removed on a rotary evaporator
  5. additionthe residue was diluted with 500 mL of water
  6. extractionextracted with methylene chloride
  7. washThe combined extracts were washed with brine
  8. dry with materialdried over MgSO4
  9. customEvaporation of the solvent

Sources & evidence

ORD record
ord-6ad111e530c8402b8eca76ffcc24dfd6
Source dataset
uspto-grants-1991_05
Patent number
US05015653

Reaction notes

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