Cepharanthine and Related Compounds. II. : A Synthesis of 1-(3-Bromo-4-methoxybenzyl)-1, 2, 3, 4-tetrahydro-6-methoxy-2-methyl-7-isoquinolinol Studies on the Syntheses of Heterocyclic Compounds. CLXXXIII

Abstract

As the starting material for the synthesis of cepharanthine, 1-(3-bromo-4-methoxybenzyl)-1, 2, 3, 4-tetrahydro-6-methoxy-2-methyl-7-isoquinolinol (IIa) was successfully prepared a different route. Anisaldehyde (VI) was derived to the ester (IX) through azlactone VII and VIII, and IX was condensed with 4-benzyloxy-3-methoxyphenethylamine (V)to form the amide (XI), which was cyclized by the usual Bischler-Napieralski reaction to form the 3, 4-dihydroisoquinoline compound (XII). Reduction of the methiodide (XIII) of XII with sodium borohydride afforded II which was found to be also obtainable by the reduction of the hydrochloride of XII with sodium borohydride, and its product submitted to the Eschweiler- Clarke reaction with formic acid and formaldehyde. Treatment of II with 2O% ethanolic hydrochloric acid afforded the debenzylated compound (IIa) as a hexane adduct. The attempted Ullmann reaction of IIa and III to obtain IV did not materialize.