Phosphoric Acid → 1-Benzyl-5-oxo-pyrrolidine-3-carboxylic acid

HRID 2304552Notes

Reaction equation

HRID 2304552 reaction equation
[CH2:1]([N:8]1[CH2:12][CH:11]([C:13]([O:15]C(C)C)=[O:14])[CH2:10][C:9]1=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.OP(O)(O)=O>O1CCOCC1.[OH-].[K+].CO>[CH2:1]([N:8]1[CH2:12][CH:11]([C:13]([OH:15])=[O:14])[CH2:10][C:9]1=[O:19])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 2

HCID 1004Phosphoric AcidHCID 18435735HCID 18435735, compound

Product 1

HCID 990241-Benzyl-5-oxo-pyrrolidine-3-carboxylic acidYield 87.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 14797Potassium HydroxideSolvent2×HCID 312751,4-DioxaneSolvent2×

Procedure

A mixture of isopropyl N-benzylpyrrolidin-2-one4-carboxylate (Example 33, 3.93 g) in dioxane (80 mL), aqueous KOH (2 N, 40 mL) and MeOH (60 mL) was stirred at room temperature for 1 hour. The mixture was then cooled with ice, acidified to pH=4 with H3PO4 and left in a refrigerator overnight. The precipitate was filtered and the filtrate was concentrated to give a yellow oil. The oil was contaminated with dioxane, and therefore was dissolved in aqueous KOH. The solution was extracted with CHCl3 (2×20 mL), and the aqueous layer was acidified with HCl (3 N). It was extracted with CHCl3 (4×30 mL). The combined extracts were dried (Na2SO4) and concentrated in vacuo to give N-benzylpyrrolidin-2-one-4carboxylic acid as a pale yellow oil (2.89 g): 1H NMR (300 MHz) δ 10.77 (br s, CO2H), 7.34 (m, 5 H), 5.17 (d, J=14.9 Hz, 1 H), 4.02 (dd, J=9.4, 3.2Hz, 1 H), 3.98 (d, J=14.1 Hz, 1 H), 2.12-2.71 (m, 4 H); 13C NMR (75 MHz) δ 176.47, 174.32, 135.25, 128.78, 128.46, 127.90, 58.63, 45.69, 29.57, 22.83; MS (FAB), m/e 220 (100, M+H), 174 (40); HRMS (FAB) m/e calcd for (C12H13NO3+H) 220.0974, found 220.0984.

Workup

  1. temperatureThe mixture was then cooled with ice
  2. waitleft in a refrigerator overnight
  3. filtrationThe precipitate was filtered
  4. concentrationthe filtrate was concentrated
  5. customto give a yellow oil
  6. extractionThe solution was extracted with CHCl3 (2×20 mL)
  7. extractionIt was extracted with CHCl3 (4×30 mL)
  8. dry with materialThe combined extracts were dried (Na2SO4)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7a0b0aab3d0747859372297ba85dff4c
Source dataset
uspto-grants-2002_08
Patent number
US06436954B1

Reaction notes

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