Diethyl Ether → 2,6-Difluoro-3-neopentylpyridine

Participants

Reaction Conditions

Reaction Steps

To a 500 mL RBF was added neopentylmagnesium chloride, 111.0M in ether (28.0 ml, 28 mmol) and an ice bath. After cooling, zinc(II) chloride, 0.5M in THF (56.0 ml, 28 mmol) was added dropwise. The cooling bath was removed and after stirring for 45 minutes, Reactant 1 (0.26 g, 0.32 mmol) was added followed by 2,6-difluoro-3-iodopyridine (2.74 g, 8.0 mmol) in THF (10 mL), which was added dropwise. The yellow solution was then heated to 60° C. After stirring overnight the reaction was allowed to cool and sat'd. NH4Cl was added cautiously. The reaction mixture was partitioned between EtOAc/Water. The aqueous layer was extracted with EtOAc (50 mL) and the combined organic layers washed with brine and concentrated in vacuo. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (40 g), eluting with 1% EtOAc in hexane, to provide 2,6-difluoro-3-neopentylpyridine as a colorless oil. MS m/z: 186 (M+1).

Provenance & Evidence