US 2025/0289784 A1 · DIROXIMEL FUMARATE SYNTHESIS

Abstract

Disclosed is a one-pot process (without the isolation of three intermediates) of preparing diroximel fumarate represented by the following structural formula: The method comprises reacting ethylene carbonate with succinimide 5 to form 2-hydroxyethyl succinimide; reacting 2-hydroxyethyl succinimide with maleic anhydride to form a (Z)-4-(2-(2,5-dioxopyrrolidin-1-yl)ethoxy)-4-oxobut-2-enoic acid intermediate, isomerizing the (Z)-4-(2-(2,5-dioxopyrrolidin-1-yl)ethoxy)-4-oxobut-2-enoic acid intermediate to an (E)-4-(2-(2,5-dioxopyrrolidin-1-yl)ethoxy)-4-oxobut-2-enoic acid intermediate, and reacting the (E)-4-(2-10(2,5-dioxopyrrolidin-1-yl)ethoxy)-4-oxobut-2-enoic acid intermediate with methanol to form the product compound.

Claims33

Dependent claims

A method of preparing a product compound represented by the following structural formula (III):

comprising the steps of:
a) reacting ethylene carbonate with succinimide to form a 2-hydroxyethyl succinimide intermediate represented by the following structural formula (I):
b) reacting the hydroxyethyl succinimide intermediate of structural formula (I) with maleic anhydride in the presence of a catalytic amount of a Lewis acid to form an (E)-4-(2-(2,5-dioxopyrrolidin-1-yl)ethoxy)-4-oxobut-2-enoic acid intermediate represented by the following structural formula (II):
and
c) reacting the (E)-4-(2-(2,5-dioxopyrrolidin-1-yl)ethoxy)-4-oxobut-2-enoic acid intermediate of formula (II) with methanol in the presence of a carboxylic acid coupling agent and an acyl transfer catalyst to form the product compound (III).

2 more elements

Dependencies are inferred from the claim text.

Diroximel fumarate synthesis

Life of this patent

Diroximel fumarate synthesis

Life of this patent

Abstract

Claims33