3-Butenoic acid → 3-(4-Cyanophenyl)isoxazolin-5-ylacetic acid

Participants

Reaction Steps

To a solution of 4-cyanobenzaldoxime (see Ex 43, Part A) (312 g, 2.13 mol) in tetrahydrofuran (3000 ml) at room temperature was added vinyl acetic acid (552 g, 6.41 mol). The yellow solution was cooled in an ice bath and sodium hypochlorite solution (5200 ml) was added in a dropwise fashion over 2h. After stirring overnight at room temperature the reaction was quenched with a 5% citric acid solution and diluted with 200 ml ether. The layers were separated and the aqueous acidified to pH 4 using citric acid. The acid layer was washed twice with 200 ml ether, the ether layers combined and extracted with saturated sodium bicarbonate solution. After acidifying the basic layer with citric acid, the product was extracted into 400 ml ether. The organic phase was washed three times with 150 ml water, once with brine, dried (MgSO4) and concentrated to give 220g of 3-(4-cyanophenyl)isoxazolin-5-ylacetic acid as a white solid. Recrystallization from 25% water/ethanol yielded 165 g of analytically pure material. Anal. Calcd for C12H10N2O3 : C,62.61; H,4.38; N, 12.17. Found: C, 62.37; H 4.47; N, 11.71. 1H NMR(300MHz, CDCl3): δ 7.77-7.76 (d, 2H, J=1.8Hz); 7.72-7.71 (d, 2H, J=1.8Hz); 5.22-5.14 (m, 1H); 3.63-3.54 (dd, 1H, J=10.6Hz, 16.8Hz); 3.19-3.11 (dd, 1H, J=7.3Hz, 16.8Hz); 3.00-2.93 (dd, 1H, J=6.2Hz, 16.5Hz); 2.79-2.72 (dd, 1H, J=7.3Hz, 16.5Hz). IR(KBr pellet): 3202, 2244, 1736, 1610, 1432, 1416, 1194, 1152, 928, 840, 562 cm-1.

Provenance & Evidence