反应详情

Tetrakis(triphenylphosphine)palladium (0.54 g, 0.48 mmol, 2.2% mol eq) was added to a degassed (nitrogen) mixture of 2-bromo-thiazole-4-carboxylic acid ethyl ester (Combi-Blocks, Inc., San Diego, Calif.; 5 g, 21.2 mmol), 1-methoxy-6-flurophenylboronic acid (4.68 g, 27.56 mmol), and sodium carbonate(23 mL, 2 M solution in water) in DME (100 mL) and DMF (100 mL). The reaction mixture was refluxed under inert atmosphere overnight. After cooling to room temperature, the reaction mixture was filtered through celite, and water and EtOAc were added. The aqueous layer was separated, acidified with conc. HCl to pH 2 and then was extracted three times with EtOAc. The combined EtOAc layers were dried under vacuum. The residue was chromatographed on silica, eluting with EtOAc/Hexane (0-30% gradient) to give 2-(2-fluoro-6-methoxy-phenyl)-thiazole-4-carboxylic acid (4.5 g) which was used directly in the next step.

1. customa degassed
2. temperatureThe reaction mixture was refluxed under inert atmosphere overnight
3. filtrationthe reaction mixture was filtered through celite, and water and EtOAc
4. additionwere added
5. customThe aqueous layer was separated
6. extractionwas extracted three times with EtOAc
7. dry with materialThe combined EtOAc layers were dried under vacuum
8. customThe residue was chromatographed on silica
9. washeluting with EtOAc/Hexane (0-30% gradient)