1,2,3,4-Tetrahydro-1-naphthalenol → 3-(1,2,3,4-Tetrahydronaphthalen-1-YL)-3H-imidazole-4-carboxylic acid methyl ester

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Reaction Steps

To a solution of 1,2,3,4-tetrahydro-1-naphthol (CAS#529-33-9, 1.00 g, 6.74 mmol), which can be prepared as described in Ollivier, R.; et al. Journal of Medicinal Chemistry, 1997, 40, 952-960, in THF (60 mL), at 0° C. is added methyl 4-imidazolecarboxylate (CAS#17325-26-7, 0.85 g, 6.74 mmol) and triphenylphosphine, followed by diisopropyl azodicarboxylate (1.36 g, 6.74 mmol). The cooling bath is then removed. After 16 hours, the solvent is evaporated in vacuo and the residue is purified by silica gel flash chromatography (elution with ethyl acetate) to give a partially purified product, which is dissolved in ethyl acetate and extracted with 1M aqueous HCl. The aqueous layer is basified to a pH of ca. 9 with 2M aqueous NaOH, and then extracted three times with dichloromethane. The organic layers are combined, dried with MgSO4, filtered, and concentrated to furnish 3-(1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid methyl ester; MS: (ESI) m/z 257.2 (M+H)+. The HNO3 salt of the title compound is prepared by dissolving the free base in methanol, followed by treatment with an excess of a 1:1 solution of HNO3—H2O. Concentration and trituration with diethyl ether and methanol, provides the nitric acid salt of 3-(1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid methyl ester; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.66-1.87 (m, 2 H), 2.11-2.33 (m, 2 H), 2.81 (dt, J=17.2, 6.5 Hz, 1 H), 2.93 (dt, J=17.2, 6.0 Hz, 1 H), 3.87 (s, 3 H), 6.33 (t, J=5.9 Hz, 1 H), 6.99 (d, J=7.6 Hz, 1 H), 7.10-7.21 (m, 1 H), 7.21-7.35 (m, 2 H), 8.34 (s, 1 H), 8.58 (s, 1 H).

Provenance & Evidence