4-(5-Oxo-2,5-dihydrofuran-3-yl)benzonitrile synthesis

Yield:58789-95-0 78%

Reaction Conditions:

with potassium fluoride;tetra-(n-butyl)ammonium iodide;trans-bis(triphenylphosphine)palladium dichloride in water;toluene; for 24 h;Heating / reflux;

Steps:

1.4

Example 4; 4-(4 '-Cyanophenyl)furan-2(5H)-one 4; A mixture containing 4-bromo-5(H)furanone (0.251 g, 1.540 mmol), 4- cyanophenylboronic acid (0.283 g, 1.887 mmol), trans- dichlorobis(triphenylphosphine)palladium (II) (0.056 g, 7.978x10^"2 mmol), tetrabutylammonium iodide (0.026 g, 7.04OxIO^"2 mmol) and potassium fluoride (0.358 g, 6.162 mmol) in toluene (10 mL) and water (10 mL) were gently refluxed for 24 h under nitrogen before the reaction mixture was allowed to cool to room temperature. Brine (50 mL) was added and the product extracted with dichloromethane (3x20 mL). The organic fractions were combined, washed with brine (3x20 mL), dried over anhydrous magnesium sulfate and evaporated to dryness under reduced pressure to give a dark brown solid. The resulting solid was chromatographed (silica gel: eluent 50:50 dichloromethane/light petroleum followed by 100% dichloromethane) to give 4-(4 '-cyanophenyl)furan-2(5H)- one 4 (0.223 g, 78%) as a pale yellow powder, dec. 227-228⁰C (ref. PDS- 1-65). UV- Vis λ_max (MeOH) 246(1330) nm; ¹H NMR (CDCl₃) δ 7.78 (dd, 2H, J= 1.9 Hz, J= 6.4 Hz, H2¹, H6¹), 7.61 (dd, 2H, J= 2.2 Hz, J= 6.4 Hz, H3', H5'), 6.51 (t, IH, J= 1.9 Hz, H3), 5.23 (d, 2H, J= 1.9 Hz, H5); ¹³C NMR (CDCl₃) δ 172.6 (C2), 161.3 (C4), 133.7 (Cl¹), 133.0 (C3¹, C5'), 127.0 (C2¹, C6'), 117.7 (C4'-CN), 116.4 (C3), 115.2 (C4¹), 70.7 (C5); IR (KBr) 3098, 2933, 2227, 1790, 1747, 1622, 1605, 1558, 1505, 1450, 1418, 1328, 1279, 1166, 1047, 993, 895, 868, 832, 706, 561, 518 cm^"1.

References:

WO2008/40097,2008,A1 Location in patent:Page/Page column 22-23