3-Oxo-azetidine-1-carboxylic acid tert-butyl ester → tert-Butyl 3-methylideneazetidine-1-carboxylate

HRID 2035656Notes

Reaction equation

HRID 2035656 reaction equation
[CH3:1]C([O-])(C)C.[K+].O=[C:8]1[CH2:11][N:10]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:9]1>CCOCC.[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]=[C:8]1[CH2:11][N:10]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:9]1

Participants

5

Reactant 2

HCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 23665647Potassium tert-butoxide

Product 1

HCID 55269097tert-Butyl 3-methylideneazetidine-1-carboxylateYield 78.7%

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 3283Diethyl EtherSolvent2×

Procedure

To a 0° C. mixture of KOtBu (5.90 g, 52.6 mmol) in 95 mL ether was added methyltriphenylphosphonium bromide (18.8 g, 52.6 mmol). The reaction mixture was warmed to ambient temperature and stirred 1.5 hours. A solution of tert-butyl 3-oxoazetidine-1-carboxylate (4.50 g, 26.3 mmol) in 10 mL ether was added. The reaction mixture was heated to reflux for 2 hours, then cooled to ambient temperature. Solids were removed by vacuum filtration through compressed Celite and rinsed with ether, and the filtrate was concentrated. The resulting residue was suspended in 1:1 hexanes:ethyl acetate, and the solids were removed by vacuum filtration through GF/F paper and rinsed with 1:1 hexanes:ethyl acetate. The filtrate was concentrated, and the resulting oil was purified on silica gel (5-20% ethyl acetate in hexanes gradient) to give the desired product (3.50 g, 78.7% yield) as a clear colorless oil.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 2 hours
  3. temperaturecooled to ambient temperature
  4. customSolids were removed by vacuum filtration
  5. washrinsed with ether
  6. concentrationthe filtrate was concentrated
  7. customethyl acetate, and the solids were removed by vacuum filtration through GF/F paper
  8. washrinsed with 1:1 hexanes
  9. concentrationThe filtrate was concentrated
  10. customthe resulting oil was purified on silica gel (5-20% ethyl acetate in hexanes gradient)

Sources & evidence

ORD record
ord-7daff68699bc4d6cb690ecc9cae1999a
Source dataset
uspto-grants-2013_11
Patent number
US08575145B2

Reaction notes

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