反应详情

温度

60 °C

A solution of 1-methyl-3-bromo-5-(nonafluorobutanesulfonyloxy)pyrazole from Step 2 (0.36 g, 0.784 mmol) and tetrakis(triphenylphosphine) palladium (0) (0.09 g, 10 mol %) in dry N,N-dimethylformamide (2 mL) was stirred under nitrogen at 60° C. for 10 min, followed by addition of a solution of 5-methylpyridin-2-ylzinc bromide in tetrahydrofuran (0.5M, 1.8 mL, 0.9 mmol). The solution was stirred at 60° C. for 18 hours then cooled, diluted with water (30 mL), and extracted with ethyl acetate (2×20 mL). The extracts were dried (Na2SO4) and concentrated. Flash column chromatography on silica, eluting with 10% ethyl acetate—isohexane, gave 1-methyl-3-bromo-5-(5-methylpyridin-2-yl)pyrazole (0.081 g, 41%) as a yellow solid. MS (ES+) 252, 254 ([MH]+). Step 4: [6S,9R,11R] 2′,3′,4′,5,5′,6,7,8,9,10-decahydro-2-(5-(5-methylprid-2-yl)-1-methyl-pyrazol-3-yl)-5′-(2,2,2-trifluoroethyl)-spiro[6,9-methanobenzocyclooctene-11,3′-[1,2,5]thiadiazole] 1′,1′-dioxide

1. temperaturethen cooled
2. extractionextracted with ethyl acetate (2×20 mL)
3. dry with materialThe extracts were dried (Na2SO4)
4. concentrationconcentrated
5. washFlash column chromatography on silica, eluting with 10% ethyl acetate—isohexane