Tetrahydrofuran → 5-Fluoro-2-methylisonicotinic acid

To a solution of methyl 2-bromo-5-fluoroisonicotinate (1.0 g, 4.27 mmol) in tetrahydrofuran (25 ml) tetrakis(triphenylphosphine)palladium (495.0 mg, 0.43 mmol) was added. The mixture was stirred for 10 min, and then trimethylaluminum (5.13 ml, 1.00 M in heptane, 5.13 mmol) was added. The mixture was refluxed for 4 h, and the reaction was monitored by TLC (10% EtOAc-Hexane). Then, the reaction was diluted with EtOAc (75 ml) and a few drops of saturated. ammonium chloride were added. The mixture was filtered through a small silica gel pad, followed by removal of the solvent. The crude product was re-dissolved in 5N NaOH solution in water and stirred at room temperature for 2 hours. The crude product was purified on Flashmaster II to afford 250 mg of 5-fluoro-2-methylisonicotinic acid.

1. temperatureThe mixture was refluxed for 4 h
2. filtrationThe mixture was filtered through a small silica gel pad
3. customfollowed by removal of the solvent
4. dissolutionThe crude product was re-dissolved in 5N NaOH solution in water
5. stirringstirred at room temperature for 2 hours
6. customThe crude product was purified on Flashmaster II

ORD record

ord-bbf408426a4148749651e27396fc8296

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08198457B2