4-hydroxy-Bicyclo[2.2.2]octane-1-carboxylic acid

Uses

4-Hydroxy-bicyclo[2.2.2]octane-1-carboxylic acid can be used as reagent/reactant in preparation and structure activity relations of tricyclic imidazoline derivatives as potent and selective adenosine A1 receptor antagonists.

Synthesis

General procedure for the synthesis of 4-hydroxybicyclo[2.2.2]octane-1-carboxylic acid from methyl 4-bromobicyclo[2.2.2]octane-1-carboxylate: 65 mL of 10% aqueous NaOH was added to a reaction vial containing 677 mg of the product of the preparation of Step A of Example 55. The reaction mixture was placed in a 100°C oil bath and stirred for 42 hours. Upon completion of the reaction, the mixture was concentrated to 15 mL and subsequently diluted with 30 mL of 1N HCl aqueous solution. The pH of the mixture was adjusted to 1 with 12N HCl aqueous solution and then extracted with EtOAc (5 x 70 mL). The organic phases were combined, dried over anhydrous MgSO4, filtered and concentrated to give 540 mg of 4-hydroxybicyclo[2,2,2]octane-1-carboxylic acid in 89% yield. [MH]+ = 171.

References

[1] Patent: WO2006/128184, 2006, A2. Location in patent: Page/Page column 174
[2] Journal of Organic Chemistry, 1970, vol. 35, p. 917 - 923
[3] Patent: US2010/267738, 2010, A1. Location in patent: Page/Page column 34
[4] Patent: WO2012/145569, 2012, A1. Location in patent: Page/Page column 136
[5] Patent: WO2015/5901, 2015, A1. Location in patent: Page/Page column 609