Ethyl Acetate → 3-(Cyclopropylcarbamoyl)-isoxazole-4-carboxylic acid ethyl ester

HRID 2368341

Reaction equation

HRID 2368341 reaction equation
[CH:1]1([NH:4][C:5](=[O:10])[C:6](Cl)=[N:7][OH:8])[CH2:3][CH2:2]1.[CH2:11]([O:13][C:14](=[O:20])/[CH:15]=[CH:16]/N(C)C)[CH3:12].C(OCC)(=O)C>C1COCC1>[CH2:11]([O:13][C:14]([C:15]1[C:6]([C:5](=[O:10])[NH:4][CH:1]2[CH2:3][CH2:2]2)=[N:7][O:8][CH:16]=1)=[O:20])[CH3:12]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 5369162Ethyl trans-3-dimethylaminoacrylateHCID 85344446N-cyclopropyl-2-chloro-2-hydroxyimino-acetamide

Product 1

HCID 700979003-(Cyclopropylcarbamoyl)-isoxazole-4-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of N-cyclopropyl-2-chloro-2-hydroxyimino-acetamide (2 g, 12.3 mmol) and (E)-3-(dimethylamino)-acrylic acid ethyl ester (1.76 ml, 12.3 mmol) in THF (25 ml) was heated at 75° C. for 2 h. The reaction was then cooled to r.t., poured into 100 mL ethyl acetate and extracted with 1 M HCl. The aqueous layers were back-extracted with ethyl acetate. The organic phase was washed with water and brine, dried and evaporated. The product was obtained after purification by silica gel chromatography using a heptane/ethyl acetate gradient as light yellow solid (1.6 g, 58%).

Workup

  1. temperatureThe reaction was then cooled to r.t.
  2. extractionextracted with 1 M HCl
  3. extractionThe aqueous layers were back-extracted with ethyl acetate
  4. washThe organic phase was washed with water and brine
  5. customdried
  6. customevaporated
  7. customThe product was obtained
  8. customafter purification by silica gel chromatography

Sources & evidence

ORD record
ord-c0bc2d58bbb842d892b8d1461e1e93ad
Source dataset
uspto-grants-2014_04
Patent number
US08703768B2

Linked notes

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