A kind of preparation method of 1-[2-amino-1-(4-methoxyphenyl) ethyl] cyclohexanol sulfate

Abstract

The invention discloses a preparation method of 1-[2-amino-1-(4-methoxyphenyl)ethyl]cyclohexanol sulfate. The method comprises the following steps: dissolving 1-cyano-[(4-methoxyphenyl)methyl]cyclohexanol in an organic solvent, and adding a Co-NiO dual catalyst at normal temperature; replacing air in the reactor with hydrogen gas, and reacting for 2-4 hours while controlling the pressure at 0.1-0.5 MPa and the temperature at 80-140 DEG C; after the reaction finishes, cooling the reaction solution to room temperature, filtering, and dropwisely adding concentrated hydrochloric acid into the filtrate; and after finishing the dropwise addition, cooling to 0-10 DEG C, keeping the temperature to crystallize, carrying out vacuum filtration and drying to obtain the 1-[2-amino-1-(4-methoxyphenyl)ethyl]cyclohexanol sulfate. By adopting the dual catalyst Co-NiO with high catalytic activity, the method shortens the reaction time, enhances the product yield, and has the advantage of simple after-treatment steps; and thus, the technique is easier for industrial production.

Description

technical field [0001] The invention relates to a preparation method of venlafaxine hydrochloride intermediate 1-[2-amino-1-(4-methoxyphenyl)ethyl]cyclohexanol sulfate, belonging to the technical field of medicine. Background technique [0002] Venlafaxine hydrochloride (Venlafaxinehydrochloride), chemical name: 1-[2-(dimethylamine)-1-(4-methoxyphenyl)ethyl]cyclohexanol hydrochloride, molecular formula: C 17 h 28 ClNO 2 ; Molecular weight: 313.86, the structural formula is as follows: [0003] [0004] Venlafaxine hydrochloride is a phenethylamine antidepressant developed by Wyeth-Ayerst Company of the United States. Its main function is to inhibit the reuptake of 5-hydroxytryptamine and norepinephrine, and also slightly inhibit the reuptake of DA. Its main metabolite O-desvenlafaxine also has the above effects. Since its clinical application, venlafaxine hydrochloride was initially used to treat depression, and later also used to treat obsessive-compulsive disorder a...

AI Technical Summary

Problems solved by technology

In Chinese patent 200410002726.5, red aluminum is used as reducing agent to prepare 1-[2-amino-1-(4-methoxyphenyl) ethyl] cyclohexanol, and the yield is as high as 92%, but red aluminum is expensive and reactive The solvent THF is difficult to recover, and the total cost is high

Patent WO2008062138 uses expensive palladium and platinum compounds as catalysts; Chinese patent 02153015.7 uses lithium aluminum hydride as a reducing agent and aluminum trichloride as a catalyst, and post-treatment is relatively difficult; Chinese patent 200910058269.4 uses sodium borohydride or potassium borohydride, and the reaction conditions Mild, the yield is as high as 92%, but in the reaction I 2 The amount of use is large, and the total cost is high; the yield of the reduction reaction under various conditions in the patent US2004181093 is only 60-70%, and the yield is relatively low

[0008] In summary, in the currently disclosed methods for the preparation of 1-[2-amino-1-(4-methoxyphenyl)ethyl]cyclohexanol, there are expensive and dangerous reducing agents or reduction catalysts, post- Difficult to handle, low yield, etc., not suitable for large-scale production

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