Process for the preparation of 1-(thiomethyl)-cyclopropaneacetic acid
AssigneeMerck & Co., Inc.
InventorsSteven King, Brenda Pipik, David A. Conlon
Life of this patent
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Abstract
The present invention provides a novel process for the preparation of 1,1-cyclopropanedimethanol cyclic sulfite which comprises: (a) contacting 1,1-cyclopropanedimethanol with dialkylsulfite in the presence of a base; and (b) removing from the reaction mixture the alcohol reaction by-product. This process is incorporated in the additional novel processes for preparing 1-(hydroxymethyl)cyclopropaneacetonitrile and 1-(thiomethyl)cyclopropaneacetic acid.
Claims16
A process for preparing a compound of the formula ##STR4## which comprises:
- (a) contacting 1,1-cyclopropanedimethanol with dialkylsulfite in the presence of an acid or a base;
- and
- (b) removing from the reaction mixture the alcohol reaction by-product.
A process for preparing 1-(hydroxymethyl)cyclopropaneacetonitrile which comprises:
- (a) contacting 1,1-cyclopropane-dimethanol with dialkylsulfite in an inert polar organic solvent and in the presence of a base;
- (b) removing from the reaction mixture the alcohol reaction by-product;
- and
- (c) adding directly to the product of step (b) sodium cyanide and sodium iodide to provide the desired product.
A process for preparing 1-(thiomethyl)cyclopropaneacetic acid which comprises:
- (a) contacting 1,1-cyclopropanedimethanol with dialkylsulfite in an inert polar organic solvent and in the presence of a base;
- (b) removing from the reaction mixture the alcohol reaction by-product;
- (c) adding directly to the product of step (b) sodium cyanide and sodium iodide to provide 1-(hydroxymethyl)cyclopropaneacetonitrile;
- (d) converting the hydroxy group of the product of step (c) into a sulfonate leaving group;
- (e) contacting the product of step (d) with thiolacetic acid and an amine base to provide 1-(acetylthiomethyl)cyclopropaneacetonitrile;
- and
- (f) hydrolyzing the product of step (e) in a biphasic solvent system.
Dependencies are inferred from the claim text.