A suspension of magnesium turnings (2.68 g) in anhydrous tetrahydrofuran (20 mL) is cooled to 10° C. and five drops of 1,2-dibromoethane are added. 2 mL of a solution of 2-(4-bromo-phenyl)-[1,3]dioxane (24.3 g; 100 mmol) in anhydrous tetrahydrofuran (80 mL) is added at 10° C. under vigorous stirring. After the reaction starts the remainder of the solution of 2-(4-bromo-phenyl)-[1,3]dioxane is added over 90 minutes. The resulting mixture is further stirred at about 16° C. for 2 hours and at 25° C. for 75 minutes. The concentration of 4-([1,3]dioxan-2-yl)phenylmagnesium bromide in the solution above the excess of magnesium turnings is about 0.90 M. In another flask, dichloro[1,3-bis(diphenylphosphino)propane]nickel(II) (0.054 g; 0.10 mmol) is suspended in 1,2-dimethoxyethane (7.7 mL) and cooled to about 0° C. before a 0.5 M solution of zinc chloride in tetrahydrofuran (1.0 mL; 0.50 mmol) and a solution of a mixture of 5-(2-chlorophenyl)-2-(tetrahydropyran-2-yl)-2H-tetrazole and 5-(2-chlorophenyl)-1-(tetrahydropyran-2-yl)-1H-tetrazole (2.65 g; 10.0 mmol) in 1,2-dimethoxyethane (2.7 mL) are added. To the vigorously stirred resulting suspension is added at about 0° C. 13.4 mL of the above 0.90 M 4-([1,3]dioxan-2-yl)phenylmagnesium bromide solution (12.0 mmol) over one hour. The resulting brown-yellow solution is allowed to warm up and further stirred at room temperature for 3 hours. The mixture is cooled to about 0° C. and quenched with a 7.5% solution of ammonium chloride in water (20 mL). The aqueous phase is separated and extracted with ethyl acetate (50 mL). The combined organic phases are washed with water (20 mL), a 7.5 % solution of sodium carbonate in water (20 mL) and water (20 mL). The combined organic phases are evaporated in vacuo. A solution of the resulting oil in a small amount of ethyl acetate is filtered and evaporated. The resulting oil is purified by column chromatography on silica gel eluting with a 1:2 mixture of ethyl acetate and hexane to afford the main isomer (N2-isomer) 5-(4′-[1,3]dioxan-2-yl-biphenyl-2-yl2-(tetrahydro-pyran-2-yl)-2H-tetrazole as a colorless oil and the minor isomer (N1-isomer) 5-(4′-[1,3]dioxan-2-yl-biphenyl-2-yl)-1-(tetrahydro-pyran-2-yl)-1H-tetrazole as colorless crystals.
