The invention provides a method for synthesizing doxepin
hydrochloride. The method comprises the following steps of: 1, carrying out an
addition reaction on 6,11-dihydrobenz [b,e] oxepin-11-one and 3-chloropropyl-methyl tert-butyl
ether to obtain
alcohol compounds; 2, removing hydroxyl from the
alcohol compounds under the condition of concentrated
hydrochloric acid to obtain olefin compounds; 3, reacting the olefin compounds with
thionyl chloride in a reaction
solvent to obtain
chloride; 4,
coupling the
chloride with N,N-dimethyl
methylamine to obtain doxepin; and 5, preparing the doxepin into
hydrochloride of the doxepin to obtain the doxepin
hydrochloride. An Ni(OAc)2 / PPh3
system is creatively used in C-N
coupling reaction in the step 4, thus the doxepin hydrochloride has the characteristics of good reaction selectivity, high yield and environmental friendliness; and the catalyst is can be recycled after being simply filtered, thus the production cost is greatly lowered. The whole method has the advantages of simpleness in operation, and easy obtaining and low cost of raw materials, accords with the requirement of industrial production, and is expected to be industrially applied.