Ethyl Acrylate → 1-tert-Butyl 3-ethyl 4-oxopyrrolidine-1,3-dicarboxylate

HRID 456342

Reaction equation

HRID 456342 reaction equation
CO[C:3](=[O:13])[CH2:4][NH:5][C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].[C:14]([O:18][CH2:19][CH3:20])(=[O:17])[CH:15]=[CH2:16].CC([O-])(C)C.[K+]>C1COCC1>[CH2:19]([O:18][C:14]([CH:15]1[C:3](=[O:13])[CH2:4][N:5]([C:6]([O:8][C:9]([CH3:10])([CH3:11])[CH3:12])=[O:7])[CH2:16]1)=[O:17])[CH3:20]

Participants

5

Reactant 3

HCID 8821Ethyl AcrylateHCID 637609N-Boc-glycine methyl esterHCID 23665647Potassium tert-butoxide

Product 1

HCID 108689421-tert-Butyl 3-ethyl 4-oxopyrrolidine-1,3-dicarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of BOC glycine methyl ester (J. Med. Chem. 2001, 44, 8, 1192-1201) (19.2 g, 101.5 mmol) in THF at 0° C. was added dropwise ethyl acrylate (11 mL, 101.5 mmol) over 10 minutes. The solution was stirred for 20 minutes, then KOtBu (111.65 mL, 111.65 mmol) was added over 45 minutes. The solution was allowed to warm to 25° C. overnight. The resulting solution concentrated in vacuo and portioned between ethyl acetate and water containing 5 mL of acetic acid. The ethyl acetate layer was removed and aqueous layer extracted with 2×200 mL of ethyl acetate. The combined ethyl acetate layers were washed with brine, dried over MgSO4, filtered and concentrated in vacuo to afford an oil. MS (DCI/NH4) m/z=258 (M+H)+, 275 (M+NH4)+.

Workup

  1. concentrationThe resulting solution concentrated in vacuo
  2. customThe ethyl acetate layer was removed
  3. extractionaqueous layer extracted with 2×200 mL of ethyl acetate
  4. washThe combined ethyl acetate layers were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford an oil

Sources & evidence

ORD record
ord-4b15624d75e04b23acafc39493a16c7c
Source dataset
uspto-grants-2013_07
Patent number
US08497275B2

Linked notes

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