反应详情

A solution of methyl 4-bromo-5-methyl-2-thiophenecarboxylate (2 g, 8.51 mmol) [prepared in Preparation 10], potassium carbonate (5.88 g, 42.5 mmol), 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (2.124 g, 10.21 mmol) [prepared according to Preparation 7] and bis(tri-t-butylphosphine)palladium(0) (0.217 g, 0.425 mmol) in 1,4-Dioxane (35.4 ml) and H2O (7.09 ml) was stirred at 80° C. in a sealed tube for 1 h. The reaction mixture was then partitioned between H2O-DCM and the aqueous phase was washed several times with DCM. The combined organic fractions were dried over Na2SO4, concentrated and purified via column chromatography (silica, 25% EtOAc in hexanes) affording methyl 5-methyl-4-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxylate. This reaction was run in several batches (1 g, 3×2 g) which were combined for workup and purification affording the title compound (5.5 g, 78% combined yield) as a viscous yellow oil: LCMS (ES) m/e 236 (M+H)+.

1. customThe reaction mixture was then partitioned between H2O-DCM
2. washthe aqueous phase was washed several times with DCM
3. dry with materialThe combined organic fractions were dried over Na2SO4
4. concentrationconcentrated
5. custompurified via column chromatography (silica, 25% EtOAc in hexanes)