1-(5-Fluoro-3-pyridinyl)ethanone

To a solution of 5-fluoro-N-methoxy-N-methylnicotinamide (2, 6.5 g, 35.29 mmol) in tetrahydrofuran (150 mL), methyl magnesium bromide solution (56.24 mL, 105.82 mmol, 3M in diethyl ether) was added drop wise at 0 C under nitrogen atmosphere. The reaction mixture was stirred at the same temperature for 4 h. The reaction mixture was quenched with saturated ammonium chloride solution (100 mL) and extracted with ethyl acetate (2 x 100 mL). The combined organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel column chromatography using 35percent ethyl acetate in hexane to afford the title compound 1-(5-fluoropyridin-3-yl)ethan-1-one (3, 3.65 g, 74percent yield) as an off white solid. Calculated (M+H): 140.04; Found (M+H): 140.1[001234] Step A: 5-Fluoronicotinic acid (1.0 g, 7.1 mmol) was dissolved in THF (10 mL) and cooled to 0 °C. A 1.4 M solution of methylmagnesium bromide in THF:toluene (3:1) (11.2 mL, 15.6 mmol) was added drop wise to the solution. The solution was allowed to warm to room temperature. The solution was stirred at room temperature for 4 hours, upon which iN aqueous HC1 (50 mL) was slowly added. The mixture was partitioned into EtOAc (200 mL) and aqueous iN NaOH (200 mL). The organic layer was washed with brine, dried over Na2504, filtered and concentrated. The residue was chromatographed on silica, eluting with EtOAc (0percent to 50percent) in hexanes to afford 1-(5-fluoropyridin-3-yl)ethanone as a white powder (290 mg, 29percent).

Molecular Weight:139.13
XLogP3:0.6
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:139.043341977
Monoisotopic Mass:139.043341977
Topological Polar Surface Area:30
Heavy Atom Count:10
Complexity:138
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes