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

HRID 876492Notes

Reaction equation

HRID 876492 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-5a55864d06be453ea50c3e5b7cd43791
Source dataset
uspto-grants-2015_03
Patent number
US08987251B2

Reaction notes

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