Triphenylphosphine → HCID 67547481, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-hydroxy-isothiochroman-7-carbonitrile (630 mg, 3.3 mmol) in THF (20 mL) is added methyl 4-imidazolecarboxylate (CAS#17325-26-7, 460 mg, 3.6 mmol), and triphenylphosphine (909 mg, 3.4 mmol). The reaction is cooled to 0° C. and diisopropyl azodicarboxylate (0.66 mL, 3.4 mmol) is added. The reaction is permitted to warm to room temperature and stirred until LC-MS analysis indicates complete consumption of 4-hydroxy-isothiochroman-7-carbonitrile. The reaction mixture is diluted with saturated aqueous NaHCO3 and ethyl acetate. The layers are separated and the organic layer is dried with Na2SO4, filtered and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0:1 to 1:1) to provide 3-(7-cyano-isothiochroman-4-yl)-3H-imidazole-4-carboxylic acid methyl ester; MS: (ESI) m/z 300.1 (M+H). 1H NMR (400 MHz, CDCl3) δ ppm 3.08-3.23 (m, 1 H), 3.32 (dd, J=14.4, 4.0 Hz, 1 H), 3.73-4.07 (m, 2 H), 3.91 (s, 3 H), 6.46-6.61 (m, 1 H), 7.15 (d, J=8.1 Hz, 1 H), 7.46 (s, 1 H), 7.49-7.54 (m, 1 H), 7.56 (s, 1 H), 7.84 (s, 1 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-cyano-isothiochroman-4-yl)-3H-imidazole-4-carboxylic acid methyl ester.

Provenance & Evidence