Potassium Carbonate → 5-(6-(trifluoromethyl)-1H-indol-4-yl)oxazole

HRID 931005Notes

Reaction equation

HRID 931005 reaction equation
Br[C:2]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.CC1(C)C(C)(C)OB([C:23]2[O:27][C:26]([Si](C(C)C)(C(C)C)C(C)C)=[N:25][CH:24]=2)O1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.[Cl-].[NH4+].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:12][C:11]([F:14])([F:13])[C:9]1[CH:8]=[C:7]2[C:3]([CH:4]=[CH:5][NH:6]2)=[C:2]([C:23]2[O:27][CH:26]=[N:25][CH:24]=2)[CH:10]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 247292314-Bromo-6-(trifluoromethyl)-1H-indoleHCID 442243115-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(tris(propan-2-yl)silyl)-1,3-oxazole

Product 1

HCID 1183789305-(6-(trifluoromethyl)-1H-indol-4-yl)oxazoleYield 60.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 25517Ammonium ChlorideSolventHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 4-bromo-6-(trifluoromethyl)-1H-indole (300 mg), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(triisopropylsilyl)oxazole (422 mg), tetrakis(triphenylphosphine)palladium(0) (131 mg) and potassium carbonate (314 mg) in DME/water (3/0.5 mL) was stirred with microwave irradiation at 120° C. for 30 min. The reaction mixture was diluted with saturated aqueous ammonium chloride solution, and extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was dissolved in THF (5 mL), 1N hydrochloric acid (2 mL) was added thereto, and the mixture was stirred overnight at room temperature. To the reaction mixture was added saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane) to give the title compound (174 mg).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extract was washed with water and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. dissolutionThe residue was dissolved in THF (5 mL)
  6. addition1N hydrochloric acid (2 mL) was added
  7. stirringthe mixture was stirred overnight at room temperature
  8. additionTo the reaction mixture was added saturated aqueous sodium bicarbonate solution
  9. extractionthe mixture was extracted with ethyl acetate
  10. washThe extract was washed with water and saturated brine
  11. dry with materialdried over anhydrous sodium sulfate
  12. customthe solvent was evaporated under reduced pressure
  13. customThe residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane)

Sources & evidence

ORD record
ord-ba861af8ee6a4539875fe1163d0a4a76
Source dataset
uspto-grants-2016_03
Patent number
US09296746B2

Reaction notes

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