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A PROCESS FOR THE PREPARATION OF DIMETHYL FUMARATE

IP.com Disclosure Number: IPCOM000242958D
Publication Date: 2015-Sep-02
Document File: 14 page(s) / 72K

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Abstract

The present disclosure provides an improved process for the preparation of dimethyl fumarate.

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A PROCESS FOR THE PREPARATION OF DIMETHYL FUMARATE

Abstract

The present disclosure provides an improved process for the preparation of dimethyl fumarate.

Dimethyl fumarate is chemically designated as dimethyl (E) butenedioate (or) trans-1,2-ethylene-dicarboxylic acid dimethyl ester, represented by Formula I.

Formula I

PCT Publication No. WO 2012/170923 discloses a process for the preparation of dimethyl fumarate by reacting fumaric acid and methanol in the presence of sulphuric acid, wherein the obtained product has a low level of dimethyl sulfate.

U.S. Publication No. 2002/0002306 discloses a method for producing dimethyl fumarate by isomerizing dimethyl maleate using an isomerization catalyst containing a Group VIII element.

Chinese Publication No. CN 101318901 discloses a process for the preparation of dimethyl fumarate by esterifying fumaric acid with methanol in presence of cerous methanesulfonate.

Chinese Patent No. CN 1103398 provides a process for the preparation of dimethyl fumarate by reacting maleic anhydride with thiourea to obtain fumaric acid, which is then converted to dimethyl fumarate using methanol and sulphuric acid.

Chinese Publication No. CN 102757346 discloses a process for the preparation of dimethyl fumarate by esterifying fumaric acid with methanol in the presence of an acidic ionic liquid.

Oriental Journal of Chemistry, 18(2):187-190 (2002) discloses a process for the preparation of methyl esters of carboxylic acids in the presence of thionyl chloride and methanol.  The process involves the use of excess of thionyl chloride and methanol, for example, 1.25 mole equivalents of thionyl chloride and 9 equivalents of methanol for the conversion of carboxylic acid to its methyl ester.  Furthermore, the reaction is carried out at a higher temperature, i.e., at a reflux temperature, resulting in a low yield.

There is a need in the art to provide a process for the preparation of highly pure dimethyl fumarate which involves simple, less expensive raw materials, moderate reaction conditions, and minimum time.

The present disclosure provides a process for the preparation of dimethyl fumarate, wherein the process comprises:

a)      treating fumaric acid, methanol, and thionyl chloride to obtain a reaction mixture, wherein the amount of thionyl chloride is 0.4 mole equivalents to 0.6 mole equivalents with respect to the fumaric acid; and

b)      isolating dimethyl fumarate.

Various embodiments and variants of the present disclosure are described hereinafter.

The term "about," as used herein, refers to any value which lies within the range defined by a number up to ±10% of the value.

The term “ambient temperature,” as used herein, refers to a temperature between about 20°C and about 30°C.

The term “reflux,” as used herein, refers to a process of boiling reactants in a solvent while continually condensing the vapor and returning it back to the flask as a liquid.

The term “pure dimethyl fumarate,” as used herein, refers to dim...