2-Iodothiophene → (4-Benzyloxy-1-thiophen-2-yl-cyclohexyl)dimethylamine

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Reaction Steps

4.67 g of 2-iodothiophene were dissolved in 20 ml of tetrahydrofuran, and 7.26 ml of two molar isopropylmagnesium chloride solution in tetrahydrofuran were added dropwise under a nitrogen atmosphere, while cooling with an ice bath. After one hour, 2.50 g of 4-benzyloxy-1-dimethylaminocyclohexanecarbonitrile were added dropwise, dissolved in 10 ml of tetrahydrofuran. After stirring overnight at room temperature, the mixture was again cooled in an ice bath and 25 ml of cold ammonium chloride solution (20 wt. %) were added. The phases were separated and extracted three times using 40 ml of diethyl ether each time, and the combined organic phases were dried over sodium sulfate, filtered and concentrated. The resulting crude product (3.82 g) was separated on silica gel with diethyl ether. 1.59 g of the non-polar and 260 mg of the polar diastereoisomer of (4-benzyloxy-1-thiophen-2-yl-cyclohexyl)dimethylamine were obtained and, as described for Example 1, were converted into 1.11 g (Example 11) and 210 mg (Example 12) of the corresponding hydrochlorides using chlorotrimethylsilane and water in 2-butanone.

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