Potassium Carbonate → Ethyl 6-fluoro-8-(1,3-oxazol-5-yl)imidazo[1,2-a]pyridine-3-carboxylate

HRID 931030Notes

Reaction equation

HRID 931030 reaction equation
Br[C:2]1[C:3]2[N:4]([C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:10][N:11]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.CC1(C)C(C)(C)OB([C:25]2[O:29][C:28]([Si](C(C)C)(C(C)C)C(C)C)=[N:27][CH:26]=2)O1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.O.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:8][C:6]1[CH:7]=[C:2]([C:25]2[O:29][CH:28]=[N:27][CH:26]=2)[C:3]2[N:4]([C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:10][N:11]=2)[CH:5]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 442243115-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(tris(propan-2-yl)silyl)-1,3-oxazoleHCID 118379030Ethyl 8-bromo-6-fluoroimidazo[1,2-a]pyridine-3-carboxylate

Product 1

HCID 118379034Ethyl 6-fluoro-8-(1,3-oxazol-5-yl)imidazo[1,2-a]pyridine-3-carboxylateYield 20%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of ethyl 8-bromo-6-fluoroimidazo[1,2-a]pyridine-3-carboxylate (1.0 g), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(triisopropylsilyl)oxazole (1.2 g), tetrakis(triphenylphosphine)palladium(0) (403 mg) and potassium carbonate (963 mg) in DME/water (15/4 mL) was stirred with microwave irradiation at 120° C. for 40 min. The reaction mixture was diluted with water, and extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was dissolved in THF (15 mL), and 1N hydrochloric acid (4 mL) was added thereto. The reaction mixture was stirred at room temperature for 2 hr, saturated aqueous sodium bicarbonate solution was added thereto, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane), and the obtained solid was recrystallized from ethyl acetate/hexane to give the title compound (188 mg).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe extract was dried over anhydrous magnesium sulfate
  3. customthe solvent was evaporated under reduced pressure
  4. dissolutionThe residue was dissolved in THF (15 mL)
  5. addition1N hydrochloric acid (4 mL) was added
  6. stirringThe reaction mixture was stirred at room temperature for 2 hr
  7. additionsaturated aqueous sodium bicarbonate solution was added
  8. extractionthe mixture was extracted with ethyl acetate
  9. dry with materialThe extract was dried over anhydrous magnesium sulfate
  10. customthe solvent was evaporated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)
  12. customthe obtained solid was recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-973a6a250fe24c7dad8f6e5c3cc26d40
Source dataset
uspto-grants-2016_03
Patent number
US09296746B2

Reaction notes

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