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[Working example 1] Process of 2-(2-fluoro-4-biphenyl) propionic acid methyl ester
It is 4-bromo-2-fluorobiphenyl (Aldrich Chem.Co. company make; 4.52 g) the bottom of a nitrogen atmosphere, and in piece 437 mg (18mmol) and 18 ml of tetrahydrofurans of metal magnesium. The solution which dissolved 18mmol in 18 ml of tetrahydrofurans was stirred after dropping at the room temperature for 3 hours, and the Grignard reagent was adjusted.
It is 2-bromopropionic acid methyl ester (made in Tokyo Chemicals; 3.1 g) in 18 ml of bottom tetrahydrofurans of a nitrogen atmosphere with another container on the other hand previously. 18mmol was dissolved, nickel chloride (II) and a bis(triphenyl phosphine)complex (made in Tokyo Chemicals; 117 mg, 0.18mmol) were added as a catalyst, and it cooled at -30 degrees C. The Grignard reagent tetrahydrofuran solution of the 4-bromo-2-fluorobiphenyl acquired by the above-mentioned method to this was added controlling important point sustaining temperature at -26 degree-C--24 degree C. After continuing stirring for 10 minutes, the ammonium chloride aqueous solution was added, and ethyl acetate was added and extracted. 3.6 g (78% of yield) of 2-(2-fluoro-4-biphenyl) propionic acid methyl ester was obtained by washing, drying and condensing an ethyl acetate extract with a salt solution, and refining with silica gel column chromatography.
1H-NMR (CDCl3, deltappm)
7.1-7.6(8H,m),3.8(1H,q,J=7Hz),3.7(3H,s),1.5(3H,d,J=7Hz)
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