4-Chloro-2-fluorobenzonitrile → 4-Chloro-2-ethoxybenzonitrile

To a solution of 4-chloro-2-fluoro-benzonitrile (1 g, 6.428 mmol) in ethanol (10 mL) were added sodium ethoxide solution (4.8 mL, 12.86 mmol, 21% wt in ethanol). The reaction mixture was heated at gently reflux for 12 h. The solvent was removed and the residue was partitioned between water (10 mL) and diethyl ether (20 mL). The layers were separated and the product was extracted with diethyl ether (20 mL). The organic layers were washed with brine (5 mL) and dried over anhydrous sodium sulfate. The solid was filtered off, and the filtrate was concentrated in vacuo. Purification of the residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel) eluting with 5% ethyl acetate in hexanes yielded 4-chloro-2-ethoxy-benzonitrile (670 mg, 57%).

1. temperatureThe reaction mixture was heated
2. temperatureat gently reflux for 12 h
3. customThe solvent was removed
4. customthe residue was partitioned between water (10 mL) and diethyl ether (20 mL)
5. customThe layers were separated
6. extractionthe product was extracted with diethyl ether (20 mL)
7. washThe organic layers were washed with brine (5 mL)
8. dry with materialdried over anhydrous sodium sulfate
9. filtrationThe solid was filtered off
10. concentrationthe filtrate was concentrated in vacuo
11. customPurification of the residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel)
12. washeluting with 5% ethyl acetate in hexanes

ORD record

ord-8f1a8e2402614a65a3f5690872cfe970

Source dataset

uspto-grants-2003_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06617346B1