Triphenylphosphine → 3-(7-methoxy-2,2-dimethyl-4-oxo-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester

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Reaction Conditions

Reaction Steps

To a solution of 6-methoxy-4-hydroxy-3,3-dimethyl-3,4-dihydro-2H-naphthalen-1-one (0.75 g, 3.28 mmol), isopropyl 4-imidazolecarboxylate (0.36 g, 2.30 mmol), which can be prepared as described in Example 1, in THF (20 mL) at 0° C. is added triphenylphosphine (0.87 g, 3.28 mmol), followed by dimethyl azodicarboxylate (40% in toluene, 1.2 mL, 3.28 mmol) and the cooling bath is removed. After 16 hours, the mixture is diluted with ethyl acetate and washed twice with half-saturated brine. The mixture is extracted five times with 1M aqueous HCl (20 mL portions). The acidic aqueous phases are then cooled to 0° C., the pH is adjusted to ca. 9 with 2M aqueous NaOH at 0° C. and the aqueous phase is extracted three times with dichloromethane. The combined organic phases are dried over MgSO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (dichloromethane-methanol, 99:1 to 49:1) to give 3-(7-methoxy-2,2-dimethyl-4-oxo-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester; MS: (ESI) m/z 357.1 (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-(7-methoxy-2,2-dimethyl-4-oxo-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester 1H NMR (400 MHz, MeOD) δ ppm 1.00 (s, 3 H), 1.23 (s, 3 H), 1.48 (d, J=6.3 Hz, 3 H), 1.50 (d, J=6.3 Hz, 3 H), 2.61 (d, J=17.4 Hz, 1 H), 2.78 (d, J=17.4 Hz, 1 H), 3.89 (s, 3H), 5.34-5.47 (m, 1 H), 6.85 (d, J=2.3 Hz, 1 H), 6.95 (s, 1 H), 7.20 (dd, J=8.6, 2.3 Hz, 1 H), 8.16 (d, J=8.6 Hz, 1 H), 8.40 (s, 1 H), 8.94 (s, 1 H).

Provenance & Evidence