Triethyl phosphonoacetate → tert-Butyl 3-(2-ethoxy-2-oxoethylidene)azetidine-1-carboxylate

HRID 1920849Notes

Reaction equation

HRID 1920849 reaction equation
C(OP([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])(OCC)=O)C.[H-].[Na+].O=[C:18]1[CH2:21][N:20]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:19]1>C1COCC1>[CH2:13]([O:12][C:10](=[O:11])[CH:9]=[C:18]1[CH2:19][N:20]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:21]1)[CH3:14]

Participants

5

Reactant 3

HCID 13345Triethyl phosphonoacetateHCID 24758Sodium hydrideHCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 44195530tert-Butyl 3-(2-ethoxy-2-oxoethylidene)azetidine-1-carboxylateYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To an ice-cold solution of ethyl 2-diethoxyphosphorylacetate (25.9 g, 116 mmol) in THF (200 mL) was added carefully NaH (60% dispersion in mineral oil, 4.62 g, 116 mmol) over 25 min. The cold bath was removed and after 30 min, tert-butyl 3-oxoazetidine-1-carboxylate (9.88 g, 57.7 mmol) in THF (40 mL) was added over 5 min. After 30 min, the reaction mixture was quenched with water and extracted twice with ethyl acetate. The combined organics were washed with brine, dried (MgSO4), filtered and concentrated. Purification by column chromatography (6/1 Pet ether/ethyl acetate) gave the ester (8.59 g, 62%) as a colourless oil.

Workup

  1. customThe cold bath was removed and after 30 min
  2. customthe reaction mixture was quenched with water
  3. extractionextracted twice with ethyl acetate
  4. washThe combined organics were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by column chromatography (6/1 Pet ether/ethyl acetate)

Sources & evidence

ORD record
ord-07ac4558e2994374af1de8c714203b90
Source dataset
uspto-grants-2012_05
Patent number
US08173635B2

Reaction notes

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