Synthesis
General procedure for the synthesis of 2-adamantanone-5-carboxylic acid from methyl 5-formate-2-adamantanone: To a mixture of 1.92 g (9.22 mmol) of methyl 5-formate-2-adamantanone (for preparation, see US20050245534) in THF (9 mL) and methanol (3 mL), an aqueous solution of 3N sodium hydroxide (6.15 mL. 18.4 mmol). The reaction mixture was stirred at room temperature for 16 hours. Upon completion of the reaction, methanol and THF were removed by concentration. the residue was cooled in an ice bath and the pH was adjusted slowly by addition of 6N aqueous HCl solution to about 1. After continued stirring for 30 min, the precipitate was collected by filtration, washed with water and partially dried over a filter. The resulting solid was dissolved in dichloromethane (400 mL) and dried by adding anhydrous sodium sulfate. After filtration, the filtrate was concentrated and dried under vacuum to give 1.50 g (84% yield) of 2-adamantanone-5-carboxylic acid as a white solid.HPLC analysis (Condition B): retention time 1.61 min.LCMS analysis (Condition B): m/z 193.3 [M+H]+.
References
[1] Patent: WO2012/125886, 2012, A1. Location in patent: Page/Page column 93
[2] Chemical and Pharmaceutical Bulletin, 1982, vol. 30, # 1, p. 67 - 73
[3] Patent: WO2009/156092, 2009, A2. Location in patent: Page/Page column 49
