反应详情

温度

92.5 °C

85 mg (0.38 mmol, 0.05 eq) of palladium acetate are added to a mixture of 2.50 g (7.6 mmol, 1 eq) of methyl (E)-3-(3-fluoro-4-trifluoromethanesulfonyloxyphenyl)acrylate, 3.71 g (9.9 mmol, 1.3 eq) of 3-heptyl-1-methyl-1-[3-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]urea (prepared as in Example 1e), 272 mg (0.78 mmol, 0.1 eq) of 2-(dicyclohexylphosphino)biphenyl and 5.5 mL of 2M potassium phosphate solution in 28 ml of dimethylformamide. The reaction mixture is heated at 90-95° C. overnight. The reaction medium is hydrolyzed in saturated ammonium chloride solution and extracted with ethyl acetate. The organic phases are combined, washed with water and dried over sodium sulfate. The solvent is evaporated off and the brown paste obtained (4.16 g) is chromatographed on silica gel (120 g CombiFlash column) eluted with 80/20 heptane/ethyl acetate. 706 mg (22%) of a “cis/trans” mixture are obtained. This solid is washed in an ethyl ether/heptane mixture, filtered and dried. 238 mg of methyl (E)-3-[2-fluoro-3′-(3-heptyl-1-methylureido)biphenyl-4-yl]acrylate in the form of a white solid are obtained. Yield=7%

1. extractionextracted with ethyl acetate
2. washwashed with water
3. dry with materialdried over sodium sulfate
4. customThe solvent is evaporated off
5. customthe brown paste obtained (4.16 g)
6. customis chromatographed on silica gel (120 g CombiFlash column)
7. washeluted with 80/20 heptane/ethyl acetate
8. custom706 mg (22%) of a “cis/trans” mixture are obtained
9. washThis solid is washed in an ethyl ether/heptane mixture
10. filtrationfiltered
11. customdried