Potassium Phosphate, Tribasic → methyl(E)-3-[2-fluoro-3'-(3-heptyl-1-methylureido)biphenyl-4-yl]acrylate

Participants

Reaction Conditions

Reaction Steps

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%

Provenance & Evidence