Hydrochloric Acid → (-)-2-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethylamine

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Reaction Steps

To a solution of 0.93 g (2.3 mmol) (+) or (−)-2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-acetamide in tetrahydrofuran were added 0.29 ml (2.3 mmol) boron trifluoride ethyl etherate. The mixture was stirred for 5 min. and then 4.61 ml (4.61 mmol) borane THF complex (1M solution in tetrahydrofuran) were added dropwise. The mixture was stirred at 50° C. for 55 h. The solution was poured onto 12 ml tetrahydrofuran and 5 ml methanol (gas evolution) and stirred for 1 h. Then 50 ml 1M aqueous hydrochloric acid were added and the layers were separated. The aqueous phase was extracted twice with ethyl acetate and the combined organic layers were washed with 10 ml 1M aqueous hydrochloric acid. The combined aqueous layers were adjusted to pH 10 using 32% aqueous sodium hydroxide and 1M aqueous sodium hydroxide solution. The turbid mixture was extracted three times with dichloromethane. The organic layers were washed with brine, dried over magnesium sulfate and evaporated to dryness. White foam (22%). MS (Turbo Spray): m/z=390.3 [M+H].

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