Ethyl cyanoacetate → Tert-butyl 3-(1-cyano-2-ethoxy-2-oxoethyl)azetidine-1-carboxylate

HRID 714889Notes

Reaction equation

HRID 714889 reaction equation
O=[C:2]1[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]1.C[C:14]1[NH:15]C(C)=C(C(OCC)=O)C[C:19]=1[C:20]([O:22][CH2:23][CH3:24])=[O:21].C(CC(OCC)=O)#N.N1CCC[C@H]1C(O)=O>CS(C)=O>[C:14]([CH:19]([CH:2]1[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]1)[C:20]([O:22][CH2:23][CH3:24])=[O:21])#[N:15]

Participants

6

Reactant 4

HCID 7764Ethyl cyanoacetateHCID 70849Hantzsch esterHCID 145742L-ProlineHCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 117840757Tert-butyl 3-(1-cyano-2-ethoxy-2-oxoethyl)azetidine-1-carboxylateYield 81.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of tert-butyl 3-oxoazetidine-1-carboxylate (3.4 g), diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate (5.0 g) and ethyl cyanoacetate (2.2 g) in dimethylsulfoxide (40 mL) was added L-proline (460 mg), and the mixture was stirred at room temperature for 48 hr. The insoluble substance was removed by filtration, saturated aqueous ammonium chloride solution was added thereto, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (4.3 g).

Workup

  1. customThe insoluble substance was removed by filtration, saturated aqueous ammonium chloride solution
  2. additionwas added
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe obtained organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-e40e4050e81843c69cb3000c8b1e82f3
Source dataset
uspto-grants-2015_11
Patent number
US09187453B2

Reaction notes

Loading…