3-Chlorophenol → 2-(3-(3-Chlorophenoxy)azetidin-1-yl)-5-fluoronicotinic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-chlorophenol (0.035 ml, 0.328 mmol) in dimethylformamide (1 ml), potassium carbonate (45.42 mg, 0.328 mmol) and the reaction mixture was stirred 2 h at 80° C. Methyl 5-fluoro-2-(3-((methylsulfonyl)oxy)azetidin-1-yl)nicotinate (D71) (100 mg, 0.328 mmol) was added and the resulting reaction mixture was heated 12 h at 160° C. After cooling at room temperature 1N NaOH (0.656 ml, 0.656 mmol) was added and the reaction mixture heated 2 h at 120° C. Solvents were evaporated in vacuo and the residue was loaded on SPE-SCX cartridge (5 g). Ammonia fractions after solvent evaporation afforded a residue that was further purified by Biotage column SNAP-C18 (30 g) eluting with water/acetic acid (0.1%)/acetonitrile-acetic acid (0.1%) from 70/30 to 0/100.

Provenance & Evidence