Ammonium Chloride → HCID 86638494, compound

Participants

Reaction Conditions

Reaction Steps

A solution of ethyl bromodifluoromethylphosphonate (3.2 g, 12.1 mmol) in tetrahydrofuran (20 mL) was added dropwise to a solution of isopropylmagnesium chloride (2 M in tetrahydrofuran) (6.1 mL, 12.1 mmol) in tetrahydrofuran (20 mL) at −78° C. After stirring at −78° C. for 5 min, a solution of 2,3-difluoro-4-(5-fluoropyridin-2-yl)benzaldehyde (1.92 g, 8.1 mmol) in tetrahydrofuran (20 mL) was added dropwise. After stirring for a further 5 min at −78° C. then a further 1 h between −78 and 0 then a further 1 h between 0 and ambient temperature. The reaction mixture was poured into saturated ammonium chloride and extracted with methylene chloride. Combined extracts were washed with saturated aqueous sodium bicarbonate, dried (sodium sulfate) and concentrated in vacuo to afford a slightly yellow oil. Chromatography over silica eluting with 0-40% acetone/methylene chloride afforded diethyl {2-[2,3-difluoro-4-(5-fluoropyridin-2-yl)phenyl]-1,1-difluoro-2-hydroxyethyl}phosphonate as an off-white solid.

Provenance & Evidence