Process for preparation of dimethyl-(e)-butenedioate

Patent metadata

Field	Value
Publication number	US-2016326087-A1
Application number	US-201415110104-A
Country	US
Kind code	A1
Filing date	Oct 18, 2014
Priority date	Jan 24, 2014
Publication date	Nov 10, 2016
Grant date	—

Abstract

The present invention relates to a process for preparation of dimethyl-(E)-butenedioate(I).

The process for preparation of dimethyl-(E)-butenedioate (I), comprises reaction of Fumaric acid with methanol in the presence of C 2 -C 4 alkanoyl halideas coupling catalyst.

First claim

1 . A process for the preparation of dimethyl-(E)-butenedioate(I),

comprising the steps of:
a) providing a solution of Fumaric acid in methanol at room temperature;
b) adding coupling catalyst C 2 -C 4 alkanoyl halide to the reaction mixture;
c) raising the temperature of reaction mixture up to a range of 50-75° C.;
d) cooling the reaction mixture;
e) isolating the solid material; and
f) optionally treating the solid material obtained in step e) with an organic solvent or a mixture thereof, and recovering the crystalline solid.

2 . A process for the preparation of dimethyl-(E)-butenedioate(I) according to claim 1 , wherein, in step a) solution of Fumaric acid is provided in 5-10 volumes of methanol (in mL) w.r.t. weight of Fumaric acid (in g).

3 . A process for the preparation of dimethyl-(E)-butenedioate(I) according to claim 1 , wherein, coupling catalyst C 2 -C 4 alkanoyl halide is selected from acetyl chloride or acetyl bromide, and is used in quantity of 0.35-0.5 moles per mole of Fumaric acid.

4 . A process for the preparation of dimethyl-(E)-butenedioate(I) according to claim 1 , wherein, in step c) reaction mixture temperature is raised up to 60-70° C.

5 . A process for the preparation of dimethyl-(E)-butenedioate(I) according to claim 1 , wherein, optional step f) comprises treatment of the solid material obtained in step e) with C 1 -C 3 alcoholic solvent and involves the steps of—
i. providing a solution of solid material obtained in step e) with 8-15 volume C 1 -C 3 alcoholic solvent selected from methanol, ethanol or n-propanol;
ii. heating the reaction mixture to temperature of 50-60° C.;
iii. cooling the reaction mixture to a temperature of 0-15° C.; and
iv. recovering the crystalline solid.

6 . (canceled)

7 . Crystalline dimethyl-(E)-butenedioate(I) characterized by X-ray powder diffraction pattern-having at least five 2θ° peaks selected from the XRPD peak set of 9.82, 10.88, 17.44, 19.81, 23.71, 23.97, 26.17, 33.26 and 41.26±0.1°; or substantially according to FIG.- 1 and DSC isotherm comprising at least one endothermic peak ranging between—
a. Peak-1—Between 100 to 110° C.; or
b. Peak-2—Between 135 to 155° C.

8 . A process for the preparation of dimethyl-(E)-butenedioate(I) characterized by X-ray powder diffraction pattern-having at least five diffraction angle peaks (2θ°) selected from the XRPD peak set of 9.82, 10.88, 17.44, 19.81, 23.71, 23.97, 26.17, 33.26 and 41.26±0.1° and DSC isotherm comprising at least one endothermic peak ranging between 100 to 110° C. (peak-1); and 135 to 155° C. (peak-2) comprising the steps of
a) providing a solution of Fumaric acid in methanol at room temperature;
b) adding coupling catalyst C 2 -C 4 alkanoyl halide to the reaction mixture;
c) raising the temperature of reaction mixture up to a range of 50-75° C.;
d) cooling the reaction mixture;
e) isolating the solid material;
f) providing a solution of solid material obtained in step e) with 8-15 volume C 1 -C 3 alcoholic solvent;
g) heating the reaction mixture to temperature of 50-60° C.;
h) cooling the reaction mixture to a temperature of 0-15° C.; and
i) recovering the crystalline solid.

9 . Crystalline dimethyl-(E)-butenedioate(I), according to claim 8 , further characterized by moisture content of less than 0.3% w/w (Karl Fischer Analysis).

10 . Crystalline dimethyl-(E)-butenedioate (I) according to claim 8 , further characterized by presence of Monomethyl Fumarate, to an extent of 0.01% or less (by HPLC) and particle size distribution of D90=252-280 μm.

Assignees

• Shilpa Midicare Ltd
• Shilpa Medicare Ltd

Inventors

• Dr Rafiuddin
• Pipal Bhagat Raj
• Ummadi Ravindra Reddy
• Chaturvedi Akshay Kant

Classifications

• C07C67/08 Primary

  by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds · CPC title

• C07C67/52

  by change in the physical state, e.g. crystallisation · CPC title

• C07C69/60

  Maleic acid esters; Fumaric acid esters · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title