反应详情

As described for Example 120, 700 mg of a cis-trans mixture of 1-(3-fluorophenyl)-N,N-dimethylcyclohexane-1,4-diamine were reacted with 810 mg 3-(2,6-dichlorophenyl)-5-methylisoxazole-4-carboxylic acid (1 molar equivalent) and the crude product (1.86 g) was isolated. The main fraction, obtained after column chromatography on silica gel (3.0×19 cm) with 175 ml diethyl ether followed by 250 ml diethyl ether/methanol (V:V=2:1), 250 ml diethyl ether/methanol (V:V=1:1) and 100 ml methanol, of 950 mg was dissolved in 25 ml 2-butanone and 25 ml ethyl acetate and converted into the corresponding hydrochloride of the non-polar diastereoisomer of 3-(2,6-dichlorophenyl)-5-methylisoxazole-4-carboxylic acid [4-dimethylamino-4-(3-fluorophenyl)cyclohexyl]amide by adding 35 μl water, 246 μl chlorotrimethylsilane and 25 ml diisopropylether (263 mg of white solid, Mp. 248-250° C.).

1. customthe crude product (1.86 g) was isolated