| 摘要 |
The invention relates to a process for the preparation of 8-{4'-[4''-(pyrimidin-2'''-yl)piperazin-1''-yl]butyl}-8-azaspiro[4.5]d ecan e-7,9-dione {buspirone} of the formula <IMAGE> and of its hydrochlorides by hydrogenating 8-{4'-[4''-(pyrimidin-2'''-yl)piperazin-1''-yl]but-2'-ynyl}-8-azaspiro [4.5 ]decane-7,9-dione of the formula <IMAGE> in the presence of a palladium or Raney nickel catalyst in an organic solvent and optionally converting the 8-{4'-[4''-(pyrimidin-2'''-yl)piperazin-1''-yl]butyl}-8-azaspiro[4.5]d ecan e-7,9-dione into a hydrochloride, in which a solution of 8-{4'-[4''-(pyrimidin-2'''-yl)piperazin-1''-yl]but-2'-ynyl}-8-azaspiro [4.5 ]decane-7,9-dione of the formula II in an organic solvent whose concentration is at least 40% by weight is added to a suspension of the catalyst in an organic solvent, the catalyst is removed and a) the 8-{4'-[4''-(pyrimidin-2'''-yl)piperazin-1''-yl]butyl}-8-azaspiro[4.5]d ecan e-7,9-dione base of the formula I is isolated and/or b) the 8-{4'-[4''-(pyrimidin-2'''-yl)piperazin-1''-yl]butyl}-8-azaspiro[4.5]d ecan e-7,9-dione base of the formula I is treated with hydrogen chloride at 15 to 40 DEG C in ethanol or isopropanol and the 8-{4'-[4''-(pyrimidin-2'''-yl)piperazin-1''-yl]butyl}-8-azaspiro[4.5]d ecan e-7,9-dione hydrochloride melting at 188 to 191 DEG C is isolated or c) the 8-{4'-[4''-(pyrimidin-2'''-yl)piperazin-1''-yl]butyl}-8-azaspiro[4.5]d ecan e-7,9-dione base of the formula I is treated at at most 70 DEG C with hydrogen chloride in ethyl acetate or isopropanol and the 8-{4'-[4''-(pyrimidin-2'''-yl)piperazin-1''-yl]butyl}-8-azaspiro[4.5]d ecan e-7,9-dione hydrochloride melting at 201 to 203 DEG C is isolated. |
