Uses
1,2-Piperidinedicarboxylic Acid 1-(Phenylmethyl) Ester is used to prepare disubstituted azetidinones as selective inhibitors of cysteine protease cathepsin K. It is also used to synthesize 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) as the Poly(ADP-ribose) Polymerase (PARP) inhibitor for the treatment of cancer.
Synthesis
10 g of 2-piperidinecarboxylic acid was added to a 250 mL four-neck flask, dissolved in 80 g of 10% aqueous sodium hydroxide solution and stirred until completely dissolved. Subsequently, a mixture of 15.7 g of benzyl chloroformate and 25 g of 10% aqueous sodium hydroxide solution was added dropwise. The reaction was stirred continuously at room temperature for 12 hours. Upon completion of the reaction, the reaction mixture was diluted with 100 mL of ether, followed by adjusting the pH of the aqueous layer with dilute hydrochloric acid to weakly acidic. The aqueous layer was extracted three times with ether and all organic layers were combined. The organic layer was dried with anhydrous magnesium sulfate, filtered, and the organic solvent was concentrated under reduced pressure to give 19.6 g of 1-N-benzyloxycarbonyl-2-piperidinecarboxylic acid in 96.1% yield.
References
[1] Patent: US6337423, 2002, B1. Location in patent: Example 10
[2] Patent: CN105418489, 2016, A. Location in patent: Paragraph 0010; 0015
[3] Journal of Organic Chemistry, 1993, vol. 58, # 4, p. 860 - 866
[4] Journal of Chemical Research, 2008, # 8, p. 468 - 472
[5] Patent: WO2010/21797, 2010, A1. Location in patent: Page/Page column 106
