Abstract
A synthesis of rac-dihydroisorotundine (F) was described. Thus β-3, 4-dimethoxyphenethylamine, formaldehyde, and methylmalonic acid were condensed to yield 2-methyl-2-(3, 4-dimethoxyphenethylaminomethyl) malonic acid (VI) in an excellent yield, which suffered a smooth decarboxylation when boiled with hydrous acetic acid. The resultant monocarboxylic acid (VII) was esterified and then condensed with ethoxycarbonylacetyl chloride, furnishing a good yield of the amide (VIII), which was cyclized and reduced to form the isoquinoline derivative (IX). The latter underwent a smooth Dieckmann condensation, giving the β-keto ester (X) which, in conformity with its structure, was soluble in dilute sodium hydroxide solution and gave a positive ferric chloride color test. When boiled with 10% hydrochloric acid this underwent ketone fission and the resultant ketone (XI) was isolated in a fair yield, of which the corresponding dimethylketal (XII) was prepared by treating with methyl orthoformate in the presence of dry hydrogen chloride. The latter was found rather stable to heat and could be distilled without decomposition, but suffered a loss of a molecule of methanol when heated with aluminum tert-butoxide at 220°, thus furnishing rac-dihydroisorotundine (F) as a faint yellow syrup, which was characterized through its crystalline methiodide.
