反应详情

To a solution of 4-(5-hydroxymethyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one (0.56 g, 2.0 mmol) (Example 6d) in THF (10 mL) is added ethanol (0.6 mL), sodium cyanide (0.111 g, 2.26 mmol) and manganese dioxide (2.69 g, 30.9 mmol). The mixture is stirred at reflux for 2 days, filtered and concentrated in vacuo. The residue is purified by silica gel chromatography (gradient ethyl acetate in heptane, 20% to 90%) to give 3-(3,3-dimethyl-1-oxo-isochroman-4-yl)-3H-imidazole-4-carboxylic acid ethyl ester as oil; HRMS (ESI) m/z 315.1355 [(M+H)+: Calcd for C17H18N2O4: 315.1345]; 1H NMR (400 MHz, MeOD) of the HCl salt δ ppm 1.24 (s, 3 H), 1.43 (t, J=7.1 Hz, 3 H), 1.55 (s, 3 H), 4.46 (q, J=7.1 Hz, 2 H), 6.83 (s, 1 H), 7.53 (d, J=7.6 Hz, 1 H), 7.66-7.71 (m, 2 H), 7.78 (td, 1 H), 7.91 (s, 1 H), 8.26 (dd, J=7.8, 1.3 Hz, 1 H)

1. temperatureat reflux for 2 days
2. filtrationfiltered
3. concentrationconcentrated in vacuo
4. customThe residue is purified by silica gel chromatography (gradient ethyl acetate in heptane, 20% to 90%)