Preparation method of 5-bromine-2-chlorine-4'-ethyoxyl diphenylmethane

Abstract

The invention provides a preparation method of 5-bromine-2-chlorine-4'-ethyoxyl diphenylmethane. The preparation method comprises the following steps: (1) using 4-hydroxybenzaldehyde and bromoethane as raw materials, a polar solvent as a reaction solvent and inorganic base as a catalyst to react so as to prepare 4-ethoxy-benzaldehyde; (2) using hydroxylamine hydrochloride and 4-hydroxybenzaldehyde as raw materials and a hydroxyl-containing solvent as a reaction solvent to react so as to obtain oxime, and then reacting under the effect of a dehydrating agent so as to generate 4-ethoxyl benzonitrile; (3) using 4-bromaniline and 4-ethoxyl benzonitrile as raw materials, using lewis acid as a catalyst, and performing a Hoesch reaction to generate 5-bromine-2-amino-4'-ethyoxyl benzophenone; (4) performing a diazo-reaction on 5-bromine-2-amino-4'-ethyoxyl benzophenone, and then reacting with cuprous chloride to synthesize 5-bromine-2-chlorine-4'-ethyoxyl benzophenone; and (5) performing a reduction reaction on 5-bromine-2-chlorine-4'-ethyoxyl benzophenone to obtain 5-bromine-2-chlorine-4'-ethyoxyl diphenylmethane. The method is low in cost, low in environment stress and short in synthetic route.

Description

technical field [0001] The invention relates to a preparation method of 5-bromo-2-chloro-4'-ethoxydiphenylmethane. Background technique [0002] Dapagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor, C-aryl glucoside compound, chemical name: (2S, 3R, 4R, 5S, 6R )-2-[3-(4-ethoxybenzyl)-4-chlorophenyl]-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol. Dapagliflozin inhibits the reabsorption of blood sugar by inhibiting renal sodium-glucose cotransporter 2, thereby regulating blood sugar levels in the body; at the same time, it can significantly reduce the level of glycosylated hemoglobin and body weight of patients. Dapagliflozin, jointly developed by Bristol-Myers Squibb and AstraZeneca, is the second SGLT2 inhibitor approved by the US FDA for the treatment of type 2 diabetes. [0003] 5-Bromo-2-chloro-4'-ethoxydiphenylmethane is the key intermediate for the preparation of dapagliflozin. There are two main synthetic methods. One method is to use 5-bromo-2-chloro...

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Problems solved by technology

The benzylation of this process route uses AIBN, which will produce highly toxic cyanide during the reaction process and cause serious pollution, such as patent CN104478670

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