Triphenylphosphine → 3-(5-methoxy-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester

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Reaction Steps

To a suspension of 5-methoxy-1,2,3,4-tetrahydro-naphthalen-1-ol (0.150 g, 0.842 mmol) and isopropyl 4-imidazolecarboxylate (0.087 g, 0.564 mmol), which can be prepared as described in Example 1, in THF (5 mL) at 0° C. is added triphenylphosphine (0.221 g, 0.842 mmol) followed by diisopropyl azodicarboxylate (94%, 0.181 g, 0.842 mmol). After 1 hour the mixture is diluted with ethyl acetate and extracted twice with 1M aqueous HCl. The aqueous phase is basified to a pH of ca. 9 with 2M aqueous NaOH and is extracted three times with dichloromethane. The combined organic phases are dried over magnesium sulfate, filtered, and concentrated to give a colorless residue, which is purified by silica gel flash chromatography (elution with dichloromethane-methanol, 99:1) to give 3-(5-methoxy-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester; MS: (ESI) m/z 315.1 (M+H)+. The HCl salt of the title compound can be prepared by dissolution in diethyl ether, followed by treatment with an excess of 1N HCl in diethyl ether. The resulting heterogeneous solution is concentrated to furnish the HCl salt of 3-(5-methoxy-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester; 1H NMR (400 MHz, MeOD) δ ppm 1.44 (d, J=6.3 Hz, 3 H), 1.45 (d, J=6.0 Hz, 3 H), 1.62-1.72 (m, 1 H), 1.90-1.97 (m, 1 H), 2.26-2.34 (m, 2 H), 2.66-2.74 (m, 1 H), 2.95-3.02 (m, 1 H), 3.92 (s, 3 H), 5.30-5.40 (m, 1 H), 6.53 (t, J=4.7 Hz, 1 H), 6.74 (d, J=8.0 Hz, 1 H), 7.02 (d, J=8.0 Hz, 1 H), 7.27 (t, J=8.0 Hz, 1 H), 8.32 (s, 1 H), 8.56 (s, 1 H).

Provenance & Evidence