Lithium Hydroxide → 5-(6-Methoxy-1H-imidazo[4,5-c]pyridin-1-yl)-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxylic acid

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Reaction Steps

To a solution of 1.2 g of an isomeric mixture of methyl 5-(6-methoxy-3H-imidazo[4,5-c]pyridin-3-yl)-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxylate and methyl 5-(6-methoxy-1H-imidazo[4,5-c]pyridin-1-yl)-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxylate (compounds B6a and B6b) in 30 ml tetrahydrofuran were added dropwise 30 ml of a 1N solution of LiOH. The reaction mixture was stirred for 12 h at room temperature and poured into a mixture of 200 ml diethylether and 0.1 N NaOH (1:1). The organic and aqueous layers were separated and the aqueous layer was acidified with HCl until pH 2 was reached. The aqueous layer was extracted with ethyl acetate (2×50 ml). The combined organic layers were dried with MgSO4 and concentrated to dryness under vacuum. The residue was purified by preparative HPLC to yield the title compound. The structural assignment of the title compound was unequivocally established by two-dimensional 1H NMR experiments (NOESY, COSY).

Provenance & Evidence