Ethyl 4-chloroacetoacetate → Ethyl 2-(2-cyclopropyloxazol-4-yl)acetate

HRID 931150Notes

Reaction equation

HRID 931150 reaction equation
[CH:1]1([C:4]([NH2:6])=[O:5])[CH2:3][CH2:2]1.Cl[CH2:8][C:9](=O)[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12]>C1(C)C=CC=CC=1.O1CCOCC1.O>[CH:1]1([C:4]2[O:5][CH:8]=[C:9]([CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[N:6]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 2

HCID 69484Ethyl 4-chloroacetoacetateHCID 80376Cyclopropanecarboxamide

Product 1

HCID 86672106Ethyl 2-(2-cyclopropyloxazol-4-yl)acetateYield 43.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of cyclopropanecarboxamide (3.5 g, 41.46 mmol) in toluene and 1,4-dioxane (50 mL, 1:1) was added ethyl 4-chloro-3-oxobutanoate (20.0 g, 121.95 mmol). The mixture was heated to 100° C. for 18 h, then was diluted with water and extracted with ethyl acetate. The organic layer was dried and concentrated under reduced pressure. The crude material was purified via column chromatography on 100-200 mesh silica (20% ethyl acetate in petroleum ether) to afford ethyl 2-(2-cyclopropyloxazol-4-yl)acetate (3.5 g). MS (ES+APCI) 196.1; LCMS retention time: 4.029 min (Method Q1).

Workup

  1. extractionextracted with ethyl acetate
  2. customThe organic layer was dried
  3. concentrationconcentrated under reduced pressure
  4. customThe crude material was purified via column chromatography on 100-200 mesh silica (20% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-25f9f57367c54797bb0630ae93f10b31
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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