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

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).

1. customThe flask was fitted with an inert atmosphere inlet
2. waitswept with Ar for several minutes
3. temperatureThe solution was cooled
4. additiontreated with fDEAD (Fluorous Technologies, 0.41 g, 0.49 mmol)
5. customThe THF was removed
6. dissolutionthe residue was dissolved in 0.5 mL dry DMF
7. washThe cartridge was eluted with 50 mL of 70% aqueous methanol, 50 mL of 80% aqueous methanol
8. concentrationThe combined eluents were concentrated in vacuo
9. washThe silica was washed with 5 mL dry THF
10. concentrationconcentrated in vacuo
11. dissolutionThe residue was dissolved in 3 mL dry THF
12. stirringThe slurry was stirred at room temperature for 30 minutes
13. filtrationfiltered
14. washThe silica was eluted with 5 mL dry THF
15. concentrationthe combined eluents were concentrated in vacuo

ORD record

ord-1d638c1bec134b8d80a7c688378cc54c

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07928140B2