2,3-Dihydroxybenzoic Acid → 2,3-Bis(4-methoxybenzyloxy)benzoic acid

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Reaction Steps

A catechol protecting group other than methyl, that is, one that could be removed concurrently with the BOC functionality while leaving the disulfide intact, was required. Thus, 2,3-dihydroxybenzoic acid (18) was converted to its trianion with NaH in DMF and treated with excess 4-methoxybenzyl bromide to make ester 19 in 62% yield. Hydrolysis of 19 with NaOH (aqueous) in dioxane produced 2,3-bis(4-methoxybenzyloxy)benzoic acid (20) in 90% recrystallized yield (Scheme 1: Synthesis of 20a. aReagents: (a) 60% NaH, 4-methoxybenzyl bromide (3.5 equivalents), DMF, 62%; (b) 2N NaOH, dioxane, 90%). Activation of an equivalent of carboxylic acid 20 with CDI and stirring with N12-(phthaloyl)thermospermine (12) in CH2Cl2 and NEt3 afforded diamine 21 in 57% yield (FIG. 6).

Provenance & Evidence