Hydrochloric Acid → 2-Fluoro-5-neopentylpyridine

Participants

Reaction Steps

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.

Provenance & Evidence