To a solution of N,N,N′N′-tetramethylethylenediamine (1.20 g, 10.3 mmol) in diethyl ether (50 ml) at −78° C. was added 1.6M N-butyl lithium solution in n-hexane (6.40 ml, 10.3 mmol). Stirring for 1 h at −20° C. was followed by addition of 3-fluoropyridine (1.00 g, 10.3 mmol) at −78° C. After stirring at −60 to −70° C. for 3 h a solution of zinc chloride (2.81 g, 20.6 mmol), which had previously been dried by melting in vacuo followed by cooling under argon, in diethyl ether (20 ml) was added dropwise at max. −60° C. The reaction mixture was allowed to warm to room temperature 45 minutes after completed addition. Addition of tetrakis(triphenylphosphine)palladium(0) (0.59 g, 0.51 mmol) and trans-4-chlorocarbonyl-cyclohexanecarboxylic acid methyl ester (2.10 g, 10.3 mmol) was followed by stirring for 16 h. The reaction was quenched with aqueous saturated ammonium chloride solution and the mixture was extracted with three 100-ml portions of tert-butyl methyl ether. The combined organic layers were washed with one 50-ml portion of 2 M aqueous sodium carbonate solution and one 50-ml portion of brine, dried over anhydrous sodium sulfate and concentrated to dryness. Separation by flash-chromatography with n-heptane/ethyl acetate as eluent gave trans-4-(3-fluoro-pyridine-2-carbonyl)-cyclohexanecarboxylic acid methyl ester (0.22 g, 7.9%) as yellow oil and trans-4-(3-fluoro-pyridine-4-carbonyl)-cyclohexanecarboxylic acid methyl ester (0.23 g, 8.4%) as yellow solid.
