54202-05-0

The general procedure for the synthesis of methyl 4-cyanobicyclo[2.2.2]octane-1-carboxylate from methyl 4-carbamoylbicyclo[2.2.2]octane-1-carboxylate was as follows: to a solution of pyridine (10 mL) containing methyl 4-carbamoylbicyclo[2.2.2]octane-1-carboxylate (228 mg) and imidazole (147 mg) was slowly added, at 0 °C, a solution of phosphorus oxychloride (POCl3, 0.40 mL). The reaction mixture was stirred continuously at 0 °C for 1 hour. Subsequently, the reaction mixture was poured into a mixture containing ice, sodium chloride (NaCl) and ethyl acetate (EtOAc). The organic phase was separated and washed with aqueous 1N hydrochloric acid until the aqueous phase was acidic. The organic phase was dried over anhydrous magnesium sulfate (MgSO4), filtered and concentrated to afford the target product methyl 4-cyanobicyclo[2.2.2]octane-1-carboxylate (137 mg, 72% yield). Mass spectral analysis showed [MH]+ = 194.

[1] Patent: WO2006/128184, 2006, A2. Location in patent: Page/Page column 166
[2] Patent: WO2008/63671, 2008, A2. Location in patent: Page/Page column 178-179
[3] Patent: WO2008/100423, 2008, A1. Location in patent: Page/Page column 82-83