AKOS BBS-00001299 synthesis

Yield:21861-22-3 36%

Reaction Conditions:

with sodium acetate in methanol at 65; for 1 h;

Steps:

General procedure of synthesis of 6-hydroxy-1-benzofuran-3(2H)-ones 28 and 29.

General procedure: 6.8 g (0.05 mol) of zinc chloride were melted under vacuumin 500 ml 3-necked round-bottom flask. After cooling to a still-warmmelt, 50 ml of anhydrous dioxane were added and mixture was agitatedwith mechanical stirrer until full dissolution of ZnCl2. Then 0.1 mol ofcorresponding 1,3-dihydroxybenzene 24 and 25 and 9.5 ml (0.15 mol)of chloroacetonitrile were added. Flow of anhydrous hydrogen chloridewas bubbled through the mixture under stirring and cooling with icewater bath until full saturation during 4 h at a temperature below 20 °C.Mixture allowed to stay overnight, then dioxane was evapotated undervacuum, 100 ml of brine were added. Precipitate of corresponding 2,4-dihydroxy-α-chloro-acetophenone 26 or 27 was filtered and washedwith water. Wet precipitate was added to a solution of 41 g (0.3 mol) ofsodium acetate trihydrate in 250 ml of methanol and mixture was refluxedfor 1 h. Methanol was evaporated 50 ml of brine were added,precipitate of 6-hydroxy-1-benzofuran-3(2H)-ones filtered off, gentlywashed with water and dried on the air.

References:

Bdzhola, V. G.;Bilokin, Y. V.;Borysenko, I. P.;Lukashov, S. S.;Protopopov, M. V.;Prykhod'ko, A. O.;Starosyla, S. A.;Vdovin, V. S.;Yarmoluk, S. M. [Bioorganic Chemistry,2020,vol. 102] Location in patent:supporting information