Preparation method of 1-[2-amino-1-(4-methoxyphenyl)ethyl]cyclohexanol

Abstract

The invention relates to a preparation method of 1-[2-amino-1-(4-methoxyphenyl)ethyl]cyclohexanol. The preparation method is characterized by comprising the following steps: adding Raney nickel and borohydride into a reaction solvent, adding 1-[cyano(p-methoxyphenyl)methyl]cyclohexanol, performing hydrogenation reaction, filtering reaction liquid, and performing reduced pressure concentration to obtain a light yellow viscous material, namely a reaction product-1-[2-amino-1-(4-methoxyphenyl)ethyl]cyclohexanol. The preparation method has the advantages of high yield and purity, low cost, little wastewater and suitability for industrialized production.

Description

technical field [0001] The invention relates to a preparation method of 1-[2-amino-1-(4-methoxyphenyl)ethyl]cyclohexanol, in particular to a venlafaxine hydrochloride intermediate 1-[2-amino -1-(4-methoxyphenyl) ethyl] the preparation method of cyclohexanol. Background technique [0002] Venlafaxine Hydrochloride (Venlafaxine Hydrochloride) is a non-tricyclic antidepressant, the chemical name is 1-[2-dimethylamino-1-(4-methoxyphenyl)ethyl]cyclohexanol salt salt, its structural formula is: [0003] [0004] Venlafaxine is a reuptake inhibitor of serotonin, norepinephrine and dopamine, and has the advantages of rapid onset of action and few adverse reactions. And 1-[2-amino-1-(4-methoxyphenyl) ethyl] cyclohexanol is a key intermediate for the preparation of venlafaxine; [0005] The present preparation method has 1, US4535186 has reported a kind of method for preparing 1-[2-amino-1-(4-methoxyphenyl) ethyl] cyclohexanol, and this method uses 1-[cyano group (p- Methoxyphe...

AI Technical Summary

Problems solved by technology

[0005] The present preparation method has 1, US4535186 has reported a kind of method for preparing 1-[2-amino-1-(4-methoxyphenyl) ethyl] cyclohexanol, and this method uses 1-[cyano group (p- Methoxyphenyl) methyl] cyclohexanol is prepared as raw material by catalytic hydrogenation under the action of catalyst rhodium-aluminum sesquioxide, but catalyst rhodium is expensive. It is not suitable for large-scale industrial production;

[0006] 2. Chinese Journal of Pharmaceutical Industry 2004,35 (10) reported in the synthesis of venlafaxine hydrochloride with red aluminum and nickel chloride / potassium borohydride as raw material reducing agent to reduce 1-[cyano (p-methoxy Phenyl) methyl] cyclohexanol to prepare 1-[2-amino-1-(4-methoxyphenyl) ethyl] cyclohexanol, the raw materials red aluminum and nickel chloride price comparison used by these two methods High consumption is relatively large, and post-treatment produces a large amount of waste water

[0008] 4. WO03080560A1 is titled Manufacture of phenyl ethyl amine compounds in particular venlafaxine, US2004181093A1 is titled Process for preparation of phenylamine derivatives, WO2007069277A2 is titled A process for the preparation of venlafaxine hydrochloride as a catalyst for ethanol / ranylamine, etc. (methanol, butanol) solvent, catalytic hydrogenation under a certain pressure to obtain the product, but either the yield is low or the purity is not high