Condensation of 2(R)-(tosyloxymethyl)-1,4-benzodioxane (I) with 5-(3-aminopropoxy)-1,3-benzodioxole (II) by means of triethylamine in refluxing acetonitrile, followed by salification with HCl in ethyl acetate/isopropanol. (1,2)
A new synthesis of MKC-242 has been described: The tosylation of 2,2-dimethyl-1,3-dioxolane-4(R)-methanol (I) with tosyl chloride in pyridine gives the expected tosylate (II), which is condensed with pyrocatechol monobenzyl ether (III) by means of NaH in N-methylpyrrolidone (NMP) yielding 4(S)-(2-benzyloxyphenoxymethyl)-2,2-dimethyl-1,3-dioxolane (IV). The hydrolysis of the dioxolane ring with hot acetic acid affords the diol (V), which is tosylated with tosyl chloride, triethylamine and dimethylaminopyridine (DMAP) in dichloromethane to give the ditosylate (VI). The debenzylation of (VI) with H2 over Pd/C in methanol/ethyl acetate yields the phenol (VII), which is cyclized by means of K2CO3 in NMP affording 2(R)-(tosyloxymethyl)-1,4-benzodioxane (VIII). Finally, this compound is condensed with 3-(1,3-benzodioxol-5-yloxy)propylamine (IX) by means of ethyl diisopropylamine in NMP. The amine (IX) used as second starting compound has been obtained as follows: The condensation of N-(3-bromopropyl)phthalimide (X) with 5-hydroxy-1,3-benzodioxole (XI) by means of NaH in hot NMP gives N-[3-(1,3-benzodioxol-5-yloxy)propyl]phthalimide (XII), which is then treated with hydrazine in refluxing methanol to obtain amine (IX).