SYNTHESIS OF 4-(4-METHOXY-2,3,6-TRIMETHYLPHENYL)-3-BUTEN-2-ONE, A KEYSYNTHON FOR ETRETINATE AND ITS METABOLITES

A synthetic route to 4-(4-methoxy-2,3,6-trimethylphenyl)-3-buten-2-one (2), a valuable synthon to etretinate (1), a potent antipsoriatic dru g is described. The keto acids (3a) and (3b) obtained from 2,5-dimethy lanisole by acylation with methylsuccinic and succinic anhydrides, res pectively are elaborated separately to the identical methoxytrimethyld ihydronaphthalene (7a) which on ozonolysis furnishes the ring opened a rylketoaldehyde (8). Strategtic manipulation of the keto and aldehyde functions of 8 leads to the arylbutanone (14). Side chain bromination of 14 gives the bromoketone (15) which provides on dehydrobromination the key synthon (2).