Process for the preparation of cyclopropyl carboxylic acid esters and derivatives
AssigneeAstraZeneca AB
InventorsAdrian Clark, Elfyn Jones, Ulf Larsson, Anna Minidis
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Abstract
The invention relates to a novel process for the preparation of certain cyclopropyl carboxylic acid esters and other cyclopropyl carboxylic acid derivatives; a novel process for the preparation of dimethylsulfoxonium methylide and dimethylsulfonium methylide; to the use of certain cyclopropyl carboxylic acid esters in a process for the preparation of intermediates that can be used in the synthesis of pharmaceutically active entities; and to certain intermediates provided by these processes.
Claims11
A process for the preparation of a compound of formula (I):
- wherein:
- R is phenyl substituted with one or more halogen;
- and Y is OR1, where R1 is a straight chain alkyl, branched alkyl, cycloalkyl, or a substituted bicycloheptyl group;
- which comprises:
- a. chlorinating a compound of formula (Ill)
- by reaction with a chlorinating agent in the presence of an inert solvent and a catalyst at a temperature of 0–200° C.;
- and then reacting the resulting solution with YH or Y, at an elevated temperature to provIde a compound of formula (II):
- reacting a trimethylsulfoxonium salt with a solid metal hydroxide in dimethyl sulfoxide at ambient or an elevated temperature to produce dimethylsulfoxonium methylide;
- and,
- contacting the compound of formula (II) with the dimethylsulfoxonium methylide in the presence of a solvent at a temperature of −10° C.–90° C.
A process for the preparation of a compound of formula (I):
- wherein:
- R is phenyl substituted with one or more halogen;
- and Y Is OR1, where R1 is a straight chain alkyl, branched alkyl, cycloalkyl, or a substituted bicycloheptyl group;
- which comprises:
- reacting a trimethylsulfoxonium salt with a solid metal hydroxide in dimethyl sulfoxide at ambient or an elevated temperature to produce dimethylsulfoxonium methylide;
- and,
- contacting compound of formula (II)
- in which R and Y are as defined above, with the dimethylsulfoxonium methylide in the presence of a solvent at a temperature of −10° C.–90° C.
Dependencies are inferred from the claim text.