METHOD OF ISOLATION AND PURIFICATION OF (RR,SS)-2-[(DIMETHYLAMINO)METHYL]-1-(3-METHOXYPHENYL)-CYCLOHEXANOL (TRAMADOL) HYDROCHLORIDE Russian patent published in 2003 - IPC

FIELD: organic chemistry, chemical technology, pharmacy. SUBSTANCE: invention relates to improved method of isolation and purification of (RR, SS)-2-[(dimethylamino)methyl] -1-(3-methoxyphenyl)-cyclohexanol (tramadol) hydrochloride from technical mixture containing tramadol, (RS,SR)-2-[(dimethylamino)methyl] -1-(3-methoxyphenyl)cyclohexanol, [(RS,SR)-isomer] and by-side products of Grignard reaction using the selective precipitation of tramadol derivative. The parent technical mixture is treated with water in medium of water-soluble organic solvent, taken among the group of lower alcohols or ketones to yield tramadol hydrate. The preferable water content for hydrate formation is 0.1-1.0 volume parts per 1 volume part of solvent. Formed precipitate of tramadol hydrate is separated by filtration and converted to the end product by treatment with hydrogen chloride in lower alcohol or ketone or lower fatty acid lower alkyl ester medium and the following recrystallization from isopropyl alcohol. Methanol, ethanol or isopropanol are used usually as lower alcohol source. Acetone is used as lower ketone and ethyl acetate is used as lower fatty acid lower alkyl ester. Method allows to obtain product required to Pharmacopeia quality but with diminished stage numbers and number of reagents used. EFFECT: improved method of isolation. 3 cl, 1 tbl, 11 ex