Lithium Hexamethyldisilazide → 4-[5-(2-Ethoxy-vinyl)-imidazol-1-yl]-3,3-dimethyl-isochroman-1-one

Participants

Reaction Steps

To a solution of ethoxymethyltriphenylphosphonium chloride (0.426 g, 1.2 mmol) in THF (5 mL) at ambient temperature is added lithium hexamethyldisilazide (1M in THF, 1.3 mL, 1.3 mmol) and the mixture is stirred for 15 min. 3-(3,3-Dimethyl-1-oxo-isochroman-4-yl)-3H-imidazole-4-carbaldehyde (0.27 g, 1.0 mmol) (Example 9a) in THF (5 mL) and the mixture is stirred at ambient temperature overnight, then filtered. The filtrate is concentrated in vacuo to give crude 4-[5-(2-ethoxy-vinyl)-imidazol-1-yl]-3,3-dimethyl-isochroman-1-one, which is redissolved in methanol (5 mL). Pd/C (0.500 g) is added and the reaction vessel is flushed with hydrogen gas and stirred under balloon pressure at 50° C. overnight. The mixture is filtered, and the filtrate is concentrated in vacuo to give a residue which is purified by semi-preparative reverse phase HPLC to give 4-[5-(2-ethoxy-ethyl)-imidazol-1-yl]-3,3-dimethyl-isochroman-1-one as a white solid; MS (ESI) m/z 315.0 (M+H); 1H NMR (400 MHz, MeOD) of the HCl salt δ ppm 1.25 (t, J=6.9 Hz, 3 H), 1.32 (s, 3 H), 1.62 (s, 3 H), 3.29-3.37 (m, 2 H), 3.60-3.69 (m, 2 H), 3.79-3.97 (m, 2 H), 6.09 (s, 1 H), 7.57 (s, 1 H), 7.64 (d, J=7.6 Hz, 1 H), 7.73-7.79 (m, 1 H), 7.81-7.88 (m, 1 H), 8.32 (dd, J=7.7, 1.4 Hz, 1 H), 8.63 (br. s, 1H)

Provenance & Evidence