Reaktion #159664

Reaktionsgleichung

NaOH

Methyl 5-fluoro-2-(3-((methylsulfonyl)oxy)azetidin-1-yl)nicotinate

3-chlorophenol

potassium carbonate

→

2-(3-(3-chlorophenoxy)azetidin-1-yl)-5-fluoronicotinic acid

Lösungsmittel

dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe resulting reaction mixture
2. 2
   workup.ADDITIONwas added
3. 3
   Temperaturthe reaction mixture heated 2 h at 120° C
4. 4
   SonstigeSolvents were evaporated in vacuo
5. 5
   SonstigeAmmonia fractions after solvent evaporation
6. 6
   Sonstigeafforded a residue that
7. 7
   Sonstigewas further purified by Biotage column
8. 8
   Waschen(30 g) eluting with water/acetic acid (0.1%)/acetonitrile-acetic acid (0.1%) from 70/30 to 0/100

Vorschrift

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.

Quelle