5-fluoro-2-hydroxypyridine 1.844g (16.3 mmol) mixture with N-Boc-4-piperidinol 5.032g (25 mmol) and PPh3 6.82g in anhydrous THF 60mL was stirred under Ar until complete dissolution (20 min). The solution was cooled to 0C on ice bath and DEAD 40% solution in toluene 10mL (Aldrich, 26 mmol) was added dropwise over a 20 min period. The ice cooling bath was allowed to expire over 90 min and the mixture was stirred at RT for 36 hours (over weekend). The unreacted PPh3 was destroyed by addition of a small amount of concentrated H2O2 (50% solution, 0.5mL) followed by few spoons of silica. The mixture was stirred for 10 min, then filtered through a pad of silica (2x2in). The silica was washed with ethyl acetate 400mL. The combined filtrates were evaporated and the residue was dried on highvac. The residue was diluted with toluene 20mL and cyclohexane 20mL was added. The mixture was allowed to crystallize for 1 hour, the precipitate (PPh3=O) was removed by filtration (and washed with some 2:1 cyclohexane-toluene mixture), the filtrates were evaporated. The residue was dissolved in a small volume of cyclohexane-toluene 1:1 mixture, applied onto a column of silica (80g, in hexane) and eluted with ethyl acetate linear gradient, 0 to 20% EtOAc in hexane. (Combiflash LC station with UV detection). Y=4.526g (93.5%) of a white crystalline solid
1H(d6-DMSO, 400MHz): 8.126(d, 3.0Hz, 1H), 7.673(td, t:8.4Hz, 3.1Hz, 1H), 6.848(dd, 9.0Hz, 3.6Hz, 1H), 5.083(m, 1H), 3.688(dt, d:13.8Hz, t:4.6Hz, 2H), 3.145(br m, 2H), 1.928(m, 2H), 1.522(m, 2H), 1.401(s, 9H)
In this case the used phenol was much more expensive then the alcohol, so the piperidinol (and DEAD/PPh3) was used in excess.