Hydrochloric Acid → 5-(4'-dimethoxymethyl-biphenyl-2-yl)-2-(tetrahydro-pyran-2-yl)2H-tetrazole

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-(2-chlorophenyl)-2-(tetrahydropyran-2-yl)-2H-tetrazole and 5-(2-chlorophenyl) 1-(tetrahydropyran-2-yl)-1H-tetrazole (94% content; 4.22 g; 15.0 mmol; same batch as used in Example 7) is dissolved in anhydrous tetrahydrofuran (2.8 mL) under an inert atmosphere. The vigorously stirred resulting suspension is cooled to about 15° C. and a 0.96 M 4-(dimethoxymethyl)phenylmagnesium bromide solution (18 mL; 17.3 mmol; same batch as used in Example 7) is added over one hour while keeping the temperature below 25° C. by external cooling. The brown reaction mixture is agitated at room temperature for 22 hours. After that, HPLC analysis is done on a sample which is, as usual, hydrolyzed with dilute aqueous hydrochloric acid. The analysis shows mainly unconverted starting material (detected as 5-(2-chlorophenyl)-1H-tetrazole) and less than 0.25 area % of C—C-coupling product (detected as 2′-(1H-tetrazol-5-yl)biphenyl-4-carbaldehyde). Finally, when methanol (1.2 mL; 30 mmol) is added to the mixture, an unusually strong exotherm is observed which indicates that most of the 4-(dimethoxymethyl)phenylmagnesium bromide is still present after a total reaction time of 23 hours.

Provenance & Evidence