Boron tribromide → HCID 9806791, compound

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Reaction Steps

While reaction of 10a with acetic anhydride at room temperature did not give the desired 4′-acetamido derivative 13, heating 10a in acetic anhydride at reflux resulted in the diacetylation product 16 (Scheme 3). Similar diacetylation has been reported with the reaction of 2,6-dibromo-4-toluidine with refluxing acetic anhydride while lower temperatures gave a mixture of mono and diacetylated products. Ulffers, F.; von Janson, A. Diacetylderivate einger Amine der aromatischen Reihe Ber. 1894, 27, 93–101. With this in mind, mono-acetylation was accomplished by reacting 10a with 5 equivalents of acetyl chloride in the presence of 4-dimethylaminopyridine (DMAP) and triethylamine at room temperature to afford 13. Basic hydrolysis of the trifluoroacetyl protecting group of 10a and 13 gave 20c and 14, respectively. The methoxy derivatives 20c, 14, and 6c were demethylated with BBr3 to afford the desired trimetoquinol analogs 21c, 15, and 27, respectively, as hydrobromide salts (Scheme 1 and 3). In a similar manner, the 6,7-dibenzyloxy-1-(3,5-diiodo-4-methoxybenzyl)-1,2,3,4-tetrahydro-isoquinoline, Harrold, M. W.; Gerhardt, M. A.; Romstedt, K.; Feller, D. R.; Miller, D. D. Synthesis and platelet antiaggregatory activity of trimetoquinol analogs as endoperoxide/thromboxane A2 antagonists Drug Des Deliv 1987, 1, 193–207, was dealkylated with BBr3 to give 6,7-dihydroxy-1-(3,5-diiodo-4-hydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline (18) the desmethyl analog of 2. Diazotization of 10a (Scheme 3) followed by reaction of the diazonium salt with H3PO2 or potassium iodide (KI) gave the diiodo and triiodo derivatives, 19a and 19b, respectively. Basic hydrolysis of the trifluoroacetyl group of 19a,b as before gave 20a,b. Demethylation of 20a,b with BBr3 proceeded smoothly to give 21a,b. Compound 9a was acylated with acetic anhydride in refluxing benzene to give 22 which was deprotected in the same manner as 14 to give 23 (Scheme 4).

Provenance & Evidence