反应详情

To a solution of 3-(2,2-dimethyl-4-oxo-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid methyl ester, which can be prepared as described in Example 13, (985 mg, 3.31 mmol) in toluene (35 mL) at −78° C. is added a 2.0 M solution of trimethyl aluminum in toluene (3.3 mL, 6.6 mmol) followed by a 1.0 M solution of dimethyl zinc in heptane (6.6 mL, 6.6 mmol). The reaction is allowed to warm to room temperature and stirred for approximately 48 hours. The reaction is then quenched with saturated aqueous NH4Cl, and diluted with saturated aqueous NaHCO3. The reaction mixture is then extracted with dichloromethane. The organic extract is dried with Na2SO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (diethylamine-methanol-dichloromethane, 1:2:97) to furnish 3-(4-hydroxy-2,2,4-trimethyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid methyl ester as a single diastereomer; MS: (ESI) m/z 315 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 0.97 (s, 3 H), 1.04 (s, 3 H), 1.59 (br. s., 1 H), 1.65 (s, 3 H), 1.95-2.18 (m, 2 H), 3.90 (s, 3 H), 6.44 (s, 1 H), 6.76 (d, J=7.8 Hz, 1 H), 7.16-7.25 (m, 1 H), 7.37 (t, J=7.6 Hz, 1 H), 7.46 (s, 1 H), 7.66 (d, J=7.8 Hz, 1 H), 7.83 (s, 1 H);

1. customThe reaction is then quenched with saturated aqueous NH4Cl
2. additiondiluted with saturated aqueous NaHCO3
3. extractionThe reaction mixture is then extracted with dichloromethane
4. extractionThe organic extract
5. dry with materialis dried with Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe resulting residue is purified by silica gel flash chromatography (diethylamine-methanol-dichloromethane, 1:2:97)