3-[4-fluoro-3-(trifluoromethyl)phenyl]-3-oxopropanenitrile synthesis

Yield:677713-06-3 79%

Reaction Conditions:

with ammonia;sodium amide in toluene at -70; for 1 h;Cooling with acetone-dry ice;

Steps:

2 Example 2: Production of [4-fluoro-3-(trifluoromethyl)phenyl]-3-oxopropionitrile (Compound No. 2-9)

An ammonia gas was bubbled into a four-neck flask cooled in a dry ice-acetone bath to collect liquid ammonia (87 g). Thereto was added sodium amide (8.26 g, 0.212 mol) and then were added a toluene solution (10 mL) of acetonitrile (8.69 g, 0.212 mol) and a toluene solution (10 mL) of ethyl 4-fluoro-3-(trifluoromethyl)benzoate (25.0 g, 0.106 mol), followed by stirring at -70°C for 1 hour. While the reaction liquid was warmed to room temperature, the ammonia gas was released outside the system. After completion of the reaction, the reaction liquid was poured into water and extracted with toluene. The resulting aqueous layer from which insoluble matter had been removed was acidified with concentrated hydrochloric acid, followed by extraction with ethyl acetate. After the resulting extract was washed with water and saturated brine, the solvent was removed by evaporation. The resulting residue was purified on a silica gel column (Kiesel gel 60 manufactured by MERCK, 40% AcOEt-Hex) to obtain [4-fluoro-3-(trifluoromethyl)phenyl]-3-oxopropionitrile (19.4 g, 79%). ¹H-NMR (400MHz, CDCl₃): 4.13(s, 2H), 7.40(t, 1H, J=7.6Hz), 8.17(m, 1H), 8.21(d, 1H, J=7.6Hz)

References:

EP1544202,2005,A1 Location in patent:Page/Page column 36