Synthesis
General procedure for the synthesis of tert-butyl 3-oxocyclobutanecarboxylate from 3-oxocyclobutanecarboxylic acid and tert-butanol: To a solution of commercially available 3-oxocyclobutanecarboxylic acid (11.4 g, 100 mmol) in anhydrous dichloromethane (DCM, 100 mL) was added N,N'-dicyclohexylcarbodiimide (DCC, 31 g, 150 mmol) and tert-butanol (8.9 g, 120 mmol). 120 mmol). The reaction mixture was stirred at room temperature overnight. After completion of the reaction, the reaction was quenched with deionized water and the aqueous phase was extracted with DCM. The organic layers were combined, washed with saturated saline, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to afford the target product tert-butyl 3-oxocyclobutanecarboxylate (15.1 g, 89% yield).
References
[1] Patent: WO2014/131855, 2014, A1. Location in patent: Page/Page column 77
[2] Journal of Medicinal Chemistry, 2016, vol. 59, # 19, p. 8967 - 9004
[3] Journal of Organic Chemistry, 1993, vol. 58, # 1, p. 100 - 110
[4] Journal of Medicinal Chemistry, 2017, vol. 60, # 2, p. 627 - 640
[5] Patent: US2009/298894, 2009, A1. Location in patent: Page/Page column 44
