3-Bromo-5-hydroxypyridine → HCID 67097529, compound

Participants

Reaction Steps

A 5 mL, one neck round bottom flask was charged with diphenyl-[4-(1 h,1 h,2h,2h-perfluorodecyl)phenyl]phosphine (Fluorous Technologies, Pittsburgh, Pa., 0.35 g, 0.49 mmol), a stirbar, and 1 mL dry THF. The flask was fitted with an inert atmosphere inlet, and swept with Ar for several minutes. The solution was cooled using a ice-water bath, and treated with fDEAD (Fluorous Technologies, 0.41 g, 0.49 mmol) dissolved in 1 mL dry THF. After 5 minutes, (R)-(−)-5-(hydroxymethyl)-2-pyrrolidinone (0.056 g, 0.49 mmol) and 3-bromo-5-hydroxypyridine (0.0565 g, 0.32 mmol) were added in succession. The reaction warmed to room temperature over 1 h, and was stirred a total of 96 h. The THF was removed using a stream of nitrogen, and the residue was dissolved in 0.5 mL dry DMF. The solution was loaded onto a FluoroFlash® Fluorous SPE cartridge (5 g, 15 mL tube, PN 801-0058S) that had been pre-conditioned with 50 mL MeOH, followed by 50 mL 20% MeOH in water. Two additional 0.5 mL aliquots of DMF were used to quantitate the transfer. The cartridge was eluted with 50 mL of 70% aqueous methanol, 50 mL of 80% aqueous methanol. The combined eluents were concentrated in vacuo. The residue was taken up in 2 mL dry THF, and passed through 250 mg of SiO2 wet-packed with THF. The silica was washed with 5 mL dry THF, and concentrated in vacuo. The residue was dissolved in 3 mL dry THF, and treated with 0.68 mmol g−1 Si carbonate (0.48 g, 0.32 mmol). The slurry was stirred at room temperature for 30 minutes, and filtered. The silica was eluted with 5 mL dry THF, and the combined eluents were concentrated in vacuo to afford (R)-5-((5-bromopyridin-3-yloxy)methyl)pyrrolidin-2-one (0.0813 g, 92% yield). HPLC-MS: retention time=1.09 min (94.1%@215 nm; 93.2% @254 nm; m/z=271.0, calculated for C10H1179BrN2O2+H+=271.0; m/z=272.9, calculated for C10H1181BrN2O2+H+=273.0).

Provenance & Evidence