Hydrochloric Acid → 2-Fluoro-5-neopentylpyridine

To a stirred, cooled (−78° C.) solution of (1S,5S)-9-methoxy-9-bora-bicyclo[3.3.1]nonane (260 ml, 260 mmol) in THF (200 ml) was added neopentylmagnesium chloride (260 ml, 260 mmol) drop-wise. The mixture slowly warmed to RT and stirred for 3 h. The white solid was filtered off and washed thoroughly with pentane. The filtrate was concentrated to give the light yellow oil. This residue was diluted with p-dioxane (300 ml) and to this was added 5-bromo-2-fluoropyridine (35.20 g, 200 mmol), (Ph3P)4Pd (9.7 g, 8.4 mmol), and 5 N NaOH (168 ml, 838 mmol). The resulting reaction mixture was heated at 95° C. in 16 h. The mixture was cooled and added 5 N HCl (168 ml) and the reaction was stirred for 1 h and extracted with ether (3×). The organic layers were washed with brine, dried over MgSO4, concentrated and purified by ISCO (5% EtOAc/Hexanes) to give the light yellow oil. MS (m+1): 168.2.

1. filtrationThe white solid was filtered off
2. washwashed thoroughly with pentane
3. concentrationThe filtrate was concentrated
4. customto give the light yellow oil
5. customThe resulting reaction mixture
6. temperaturewas heated at 95° C. in 16 h
7. temperatureThe mixture was cooled
8. stirringthe reaction was stirred for 1 h
9. extractionextracted with ether (3×)
10. washThe organic layers were washed with brine
11. dry with materialdried over MgSO4
12. concentrationconcentrated
13. custompurified by ISCO (5% EtOAc/Hexanes)
14. customto give the light yellow oil

ORD-Eintrag

ord-e19902714dce47958481a9252dc33653

Quelldatensatz

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08163766B2