Potassium Carbonate → Ethyl 5-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methylisoxazole-3-carboxylate

HRID 1510457Notes

Reaction equation

HRID 1510457 reaction equation
[F:1][C:2]1[CH:3]=[C:4](B2OC(C)(C)C(C)(C)O2)[CH:5]=[CH:6][C:7]=1[C:8]([F:11])([F:10])[F:9].Br[C:22]1[O:26][N:25]=[C:24]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[C:23]=1[CH3:32].C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[CH:3]=[C:4]([C:22]2[O:26][N:25]=[C:24]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[C:23]=2[CH3:32])[CH:5]=[CH:6][C:7]=1[C:8]([F:9])([F:10])[F:11]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 467390543-Fluoro-4-(trifluoromethyl)phenylboronic acid pinacol esterHCID 58828802Ethyl 5-bromo-4-methyl-1,2-oxazole-3-carboxylate

Product 1

HCID 66792925Ethyl 5-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methylisoxazole-3-carboxylateYield 51.2%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Tetrakis(triphenylphosphine)palladium(0) (139 mg, 0.121 mmol) was added to a suspension of 2-(3-fluoro-4-(trifluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (350 mg, 1.21 mmol), ethyl 5-bromo-4-methylisoxazole-3-carboxylate (282 mg, 1.21 mmol) and potassium carbonate (334 mg, 2.413 mmol) in DME and water mix. The reaction mixture was sealed in a microwave vial and heated at 100° C. for 2 hours, after which time, the reaction was allowed to cool. The reaction mixture was then diluted with ethyl acetate and washed with water. The aqueous layer was then extracted with ethyl acetate, the organics combined, washed with brine and dried over magnesium sulfate, filtered and concentrated in vacuo. the resulting residue was purified by silica gel chromatography, eluting with heptane to 40% ethylacetate in heptane, to afford ethyl 5-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methylisoxazole-3-carboxylate (196 mg, 0.62 mmol).

Workup

  1. additionmix
  2. customThe reaction mixture was sealed in a microwave vial
  3. temperatureto cool
  4. washwashed with water
  5. extractionThe aqueous layer was then extracted with ethyl acetate
  6. washwashed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customthe resulting residue was purified by silica gel chromatography
  11. washeluting with heptane to 40% ethylacetate in heptane

Sources & evidence

ORD record
ord-b7e05552301844e8865bee8eeb3f915e
Source dataset
uspto-grants-2012_07
Patent number
US08211927B2

Reaction notes

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