Bicyclo[1.1.1]pentane-1,3-dicarboxylic acid is a white to off-white solid at room temperature and pressure, with significant acidity and poor chemical stability, it is insoluble in water and low-polar organic solvents but has some solvency in strong polar organic solvents. The structure of this compound contains two carboxylic acid units, with the general physical and chemical properties of alkyl carboxylic acids, which can be chlorinated under the action of dichlorosulfoxide to obtain the corresponding chloride derivatives, and can also be condensed under the action of the condensing agent and alcohol compounds to obtain the corresponding ester derivatives. In addition, it has been reported in the literature that bicyclo[1.1.1]pentane-1,3-dicarboxylic acid can be decarboxylated and fluorinated under the action of fluorinating reagent, which has better application in the synthesis of fluorinated bicyclo[1.1.1]pentane derivatives.
The general procedure for the synthesis of bicyclo[1.1.1]pentane-1,3-dicarboxylic acid using 1,1'-(bicyclo[1.1.1]pentane-1,3-diyl)diethyl ketone as a starting material was as follows: compound 4 (23 g) was dissolved in dioxane (100 mL), followed by a slow, titrational addition to a sodium hypochlorite solution (1 L) over a temperature range of 10 °C to 15 °C. The reaction mixture was stirred continuously at this temperature for 4 hours. Upon completion of the reaction, sodium thiosulfate (6 g) was added to quench the reaction. The reaction solution was washed with chloroform (400mL x 3). The aqueous phase was acidified with concentrated hydrochloric acid to pH less than 1, followed by extraction with ethyl acetate (500 mL × 3). All ethyl acetate extracts were combined, washed with saturated brine and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated to give compound 5 (11.5 g) in 50% yield.
[1] Journal of Organic Chemistry, 1988, vol. 53, # 19, p. 4593 - 4594
[2] European Journal of Organic Chemistry, 2017, vol. 2017, # 43, p. 6450 - 6456
[3] Journal of Medicinal Chemistry, 2012, vol. 55, # 7, p. 3414 - 3424
[4] Patent: CN105294442, 2016, A. Location in patent: Paragraph 0006; 0011
[5] Journal of Medicinal Chemistry, 1996, vol. 39, # 15, p. 2874 - 2876
![Bicyclo[1.1.1]pentane-1,3-dicarboxylic acid Structure](/CAS/GIF/56842-95-6.gif)
![Ethanone, 1,1-bicyclo[1.1.1]pentane-1,3-diylbis- (9CI)](/CAS/GIF/115913-30-9.gif)
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