反应详情

温度

17.5 °C

A solution of 20 g of 5′-fluoro-2′-hydroxyacetophenone (13 mol) in 100 ml of THF was slowly added at 5-10° C. to a solution of 52 ml of 30% sodium methoxide in methanol (0.30 mol). The temperature was then allowed to reach 15° C. and 22 g of diethyloxalate (0.15 mol) were added between 15 to 25° C. to give a complete solution. The reaction progress was monitored by TLC until less than 5% of raw starting material was present. The mixture was adjusted to pH 1-2 by the addition of 20 ml of 36% HCl (0.24 mol) and 100 ml of water between 5 to 15° C. The solid residue formed was removed by filtration then the aqueous layer removed by decantation. The organic layer was then washed with 40 ml of an aqueous solution of 15% NaCl and concentrated under reduced pressure at 40-50° C. to give a yellow oil. This residual oil was dissolved in 100 ml of glacial acetic acid and 100 ml of water at reflux for 17-20 h. After cooling to 15-20° C., the suspension of the title compound was filtered to give after drying 20 g of a white or off-white solid (yield: 75%). A second crop can be obtained after concentration of the mother liquor and the residue warmed up in 50 ml glacial acetic acid and 50 ml water to reflux for 20 h to hydrolyze the ester to give an additional batch of the title compound (2-3 g).

1. customto reach 15° C.
2. customto give a complete solution
3. customThe solid residue formed
4. customwas removed by filtration
5. customthe aqueous layer removed by decantation
6. washThe organic layer was then washed with 40 ml of an aqueous solution of 15% NaCl
7. concentrationconcentrated under reduced pressure at 40-50° C.
8. customto give a yellow oil