General procedure for the synthesis of 1-Boc-4-fluoro-4-(hydroxymethyl)piperidine from 1-oxa-6-azaspiro[2.5]octane-6-carboxylic acid tert-butyl ester: Commercially available epoxide (2 g, 9.38 mmol) was dissolved in 10 mL of dichloromethane, and added slowly and dropwise to a pre-cooled to -10°C 0.6 mL solution of HF pyridinium fluoride (70%) in a 10 mL dichloromethane to a mixture of 0.6 mL HF pyridinium fluoride (70%) and 10 mL methylene chloride. The reaction mixture was kept at -10°C. After the dropwise addition was completed, the reaction system was warmed to room temperature and stirred continuously for 4 hours. Upon completion of the reaction, the reaction mixture was diluted with dichloromethane and subsequently washed with saturated aqueous sodium carbonate solution. The organic phase was separated, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to remove the solvent to give the crude product. Purification by silica gel column chromatography with ethyl acetate/heptane (20% to 50%) as eluent afforded 1-Boc-4-fluoro-4-(hydroxymethyl)piperidine as a pale yellow oil (1.44 g, 66% yield).1H-NMR (400 MHz, CDCl3) data: δ=1.44 (s, 9H), 1.47-1.63 (m, 2H). 1.85 (m, 2H), 3.08 (m, 2H), 3.56 (s, 1H), 3.61 (s, 1H), 3.92 (brs, 2H). ms ESI: m/z=233.98 (M+).
![1-OXA-6-AZASPIRO[2.5]OCTANE-6-CARBOXYLIC ACID, 1,1-DIMETHYLETHYL ESTER](/CAS/GIF/147804-30-6.gif)
