Preparation of uniform racemic modifications of substituted 2-hydroxy-11bh-benzo-(a)-quinolizine derivatives

摘要

Uniform racemic modifications of a compound of the formula FORM:1063360/C2/1 and acid addition salts and quaternary ammonium compounds thereof are obtained by reacting a mixture of the two racemic forms of the compound of the above formula with sufficient malonic acid to form the hydrogen malonate acid addition salts of the said mixture of racemic forms, separating the hydrogen malonates thus obtained by means of their differential solubility in a suitable solvent such as acetone, methanol, ethanol, isopropanol or butanone or a mixture of two or more of these solvents and then treating one or both of the separated hydrogen malonates with aqueous alkali to liberate the free base which may optionally be reacted with suitable salt-forming acids or C1 to C8 alkylating agents. Pharmaceutical compositions with neuroleptic activity suitable for enteral, parenteral or topical administration comprise uniform racemates corresponding to the above general formula or physiologically compatible acid addition salts or quaternary compounds thereof in association with suitable organic or inorganic excipients. 2 - Hydroxy - 2 - ethyl - 1,2,3,4,6,7 - hexahydro-11bH-benzo[a]-quinolizine is obtained as a mixture of racemic modifications by treating 2 - oxo - 1,2,3,4,6,7 - hexahydro - 11bH - benzo-[a]-quinolizine with ethereal lithium alkyl.