Improved process for the preparation of 2- (7-methylbenzo d 1,3 dioxol-4-yl 6- (substituted)) acetic acid 2-substituted acid derivatives

摘要

A process for the preparation of 2- (7-methylbenzo [d] [1,3] dioxol-4-yl 6- (substituted)) acetic acid 2-substituted acid derivatives of formula-I, ** (See formula) * * wherein R1 is a protecting group of O which is methoxymethyl, ethoxymethyl, trialkylsilyl, arylmethyl, tetrahydropyran-2-yl or allyl; X is hydroxyl, halogen, mesylate, triflate, tosylate or acetate; And it is an oxygen atom, NH or a sulfur atom; R2 is C1-C6 alkyl comprising: (i) The reaction of 2,4-dihydroxy-3-methylbenzaldehyde with an etherification reagent in the presence of a base (or an acid in case of protection with tetrahydropyran-2-yl) and a solvent at 0-100 ° C to obtain the monoprotected derivative of formula-XII, wherein R 1 = methoxymethyl, ethoxymethyl, trialkylsilyl, tetrahydropyran-2-yl, allyl, arylmethyl (ii) Oxidation of the compound of formula-XII with an oxidizing agent in the presence of a base and a solvent at pH 7-14 to obtain the dihydroxy compound of formula-XIII, wherein R 1 = methoxymethyl , ethoxymethyl, trialkylsilyl, arylmethyl, tetrahydropyran-2-yl, allyl; (iii) The reaction of the dihydroxy compound of formula-XIII with a base and an aldehydic compound of formula -XIV, wherein Y and R2 are as defined above in the presence of a solvent a 0-100 ° C to obtain the compound of formula-XV, (iv) The reaction of the dihydroxy compound of formula-XV with a dihalomethane in the presence of a base and a solvent at 15-120 °. C to obtain the methylenedioxy derivative of formula XVI wherein R1, Y and R2 are as defined above (v) The conversion of the hydroxyl group to X wherein X is as defined above. previously defined using a suitable reagent, suitable reagent which is thionyl chloride, methanesulfonyl chloride, triflic anhydride, acetyl chloride, acetic anhydride, p-toluenesulfonyl chloride, benzenesulfonyl chloride, carbon tetrachloride / triphenylphosphine or carbon tetrabromide. triphenylphosphine, in the presence of a base a of -78 at 40 ° C to obtain the compound of formula-I wherein R1, R2, X and Y are as defined above.