Dibromomethane → tert-butyl (3RS,4RS)-4-(4-fluoro-phenyl)-3-(1-naphthalen-2-yl-vinyloxy)-piperidine-1-carboxylate

Participants

Reaction Steps

A solution of 2.7 ml (24.6 mmol) of titanium tetrachloride in 18 ml of methylene chloride was added dropwise at 0° C. under argon and with the exclusion of moisture to 30 ml of tetrahydrofuran, a yellow suspension resulting. After warming to room temperature 15 ml (95 mmol) of tetramethylethylenediamine were added and the reaction mixture was stirred for 10 minutes. After the addition of 3.6 g (55 mmol) of zinc dust the mixture was stirred at room temperature for a further 30 minutes. Thereupon, a solution of 2.1 ml (30 mmol) of dibromomethane and 2.7 g (6.0 mmol) of tert-butyl (3RS,4RS)-4-(4-fluoro-phenyl)-3-(naphthalen-2-ylcarbonyloxy)-piperidine-1-carboxylate dissolved in 30 ml of tetrahydrofuran was added dropwise in such a manner that the temperature did not rise above 36° C. Subsequently, the reaction mixture was stirred at room temperature for 60 hours, then poured into saturated ammonium chloride solution and extracted with ether. The combined ether phases were dried over magnesium sulphate, concentrated and the residue was chromatographed on silica gel using a 99:1 mixture of methylene chloride and triethylamine as the eluent. Therefrom there were obtained 1.23 g (46% of theory) of tert-butyl (3RS,4RS)-4-(4-fluoro-phenyl)-3-(1-naphthalen-2-yl-vinyloxy)-piperidine-1-carboxylate as an amorphous colourless solid; MS: 448 (M+H)+.

Provenance & Evidence