Synthesis
GENERAL STEPS: To a 100 mL round bottom flask was added tert-butyl 4-(2-ethoxy-2-oxoethoxy)piperidine-1-carboxylate (5.00 g, 17.4 mmol), sodium hydroxide (3.00 g, 75.0 mmol), water (20 mL), and ethanol (20 mL). The reaction mixture was stirred at room temperature for 48 hours. Upon completion of the reaction, the mixture was concentrated under reduced pressure to remove the solvent. The pH of the residue was adjusted with 3 mol/L hydrochloric acid solution to 2. Subsequently, the aqueous phase was extracted with ethyl acetate (2 x 20 mL), and the organic layers were combined and concentrated under reduced pressure to afford 4.00 g (89% yield) of 2-([1-[(tert-butoxy)carbonyl]piperidin-4-yl]oxy)acetic acid as an oil. Thin layer chromatography (TLC) analytical conditions: dichloromethane/methanol = 5/1, Rf = 0.4.
References
[1] Patent: WO2017/89390, 2017, A1. Location in patent: Page/Page column 97; 98
[2] European Journal of Medicinal Chemistry, 1999, vol. 34, # 5, p. 363 - 380
[3] Patent: WO2014/151958, 2014, A1. Location in patent: Paragraph 00290
