Potassium Carbonate → Methyl 5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazole-4-carboxylate

HRID 1748151Notes

Reaction equation

HRID 1748151 reaction equation
C(=O)([O-])[O-].[K+].[K+].[CH:7]1([C:10](=[O:16])[CH2:11][C:12]([O:14][CH3:15])=[O:13])[CH2:9][CH2:8]1.[F:17][C:18]([F:31])([F:30])[O:19][C:20]1[CH:29]=[CH:28][CH:27]=[CH:26][C:21]=1/[C:22](=[N:24]/O)/Cl>C1COCC1.O>[CH:7]1([C:10]2[O:16][N:24]=[C:22]([C:21]3[CH:26]=[CH:27][CH:28]=[CH:29][C:20]=3[O:19][C:18]([F:17])([F:30])[F:31])[C:11]=2[C:12]([O:14][CH3:15])=[O:13])[CH2:9][CH2:8]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 101300163-Cyclopropyl-3-Oxopropionic Acid Methyl EsterHCID 58138614N-Hydroxy-2-(trifluoromethoxy)benzimidoyl chloride

Product 1

HCID 66906029Methyl 5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazole-4-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

Potassium carbonate (11 g, 79.7 mmol, 1.09 equiv) was suspended in THF (100 mL) and the mixture was stirred. A solution of methyl 3-cyclopropyl-3-oxopropanoate (11 g, 77.5 mmol, 1.06 equiv) in 50 ml THF was added to the above stirred mixture and stirred fo(30 min at −10°C. To this reaction mixture was added a solution of (Z)-2-(trifluoromethoxy)benzoyl chloride oxime (17.6 g, 73.3 mmol, 1.00 equiv) in THF (50 mL) at −5°C. and then allowed to stir fo(6 h at 35°C. The reaction mixture was diluted with 200 mL of H2O, extracted with ethyl acetate (2×300 mL). The organic layer was washed with brine (2×200 mL), dried over anhydrous sodium sulfate, concentrated under vacuum, and then purified by silica gel column chromatography using ethyl acetate/petroleum ether (1:100-1:20) eluent to afford methyl 5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazole-4-carboxylate as a white solid.

Workup

  1. stirringstirred
  2. custom30 min
  3. customat −10°C
  4. stirringto stir
  5. custom6 h
  6. customat 35°C
  7. extractionextracted with ethyl acetate (2×300 mL)
  8. washThe organic layer was washed with brine (2×200 mL)
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated under vacuum
  11. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-06e4a66278094d468d6f111f8135256a
Source dataset
uspto-grants-2015_10
Patent number
US09150568B2

Reaction notes

Loading…