SYNTHESIS OF ARYL CYCLOHEXANE CARBOXAMIDE DERIVATIVES USEFUL AS SENSATES IN CONSUMER PRODUCTS

摘要

Synthesis methods to produce a series of carboxamides built off of an (S)-2-amino acid backbone or an (R)-2-amino acid backbone, depending upon the desired diastereomer of the end product.

主权项

1. A method for preparing an N-menthanecarboxamide derivative of the following formula (I) comprising: R1 is independently selected from H, alkyl, aryl, amino alkyl, alkoxy, alkoxy carbonyl, alkyl carbonyl, aryl carbonyl, heteroaryl carbonyl Q=H2, O, OR1, N(R1)2 V=—(CH2)mN(R1)2, O, OR1; m=0 to 6 W=H2, O X, Y=independently selected from H, alkyl, aryl, arylalkyl, cycloalkyl, naphthyl for n=0 X, Y=aliphatic CH2 or aromatic CH for n≧1 and Z is selected from aliphatic CH2, aromatic CH, or heteroatom A=lower alkoxy, lower alkylthio, aryl, substituted aryl or fused aryl and stereochemistry is variable at the positions marked*, and pharmaceutically acceptable salts thereof; A) a coupling reaction between an activated derivative of the p-menthane-3-carboxylic acid of Formula (II):wherein X=a suitable leaving group;
and a primary amine of the general formula (III): to produce a compound of the general formula (IV):