| 摘要 |
PURPOSE: Provided is a process for the industrial synthesis of the compound of formula(I) and its additional salts which can be applied to the synthesis of tianeptine and its pharmaceutically acceptable salts. CONSTITUTION: The process for the industrial synthesis of 11-amino-3-chloro-6,11-dihydro-5,5-dioxo-6-methyl-dibenzo(c,f)(1,2)thiazepine of formula(I) and its addition salts, characterized in that the ketone of formula(III) is reacted with sodium borohydride, in a two-phase medium(chlorinated solvent such as, for example, chloroform, dichloromethane or dichloroethane/aqueous sodium hydroxide solution), in the presence of N-dodecyl-N-methyl-diethanolammonium bromide, to yield the alcohol of formula(IV): which, as a suspension in a chlorinated solvent such as, for example, chloroform or dichloromethane, is treated with gaseous hydrogen chloride to yield the chloride of formula(V): which is then, without being isolated, treated with gaseous ammonia, while maintaining the temperature between 25 and 35 deg. C., to yield the compound of formula(I), which is, if desired, converted into an addition salt such as the hydrochloride.
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