[F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1.C[O-].[Na+].CO.C([O:19][C:20](=[O:26])[C:21](OCC)=O)C.Cl>C1COCC1.C(O)(=O)C.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:11][C:21]([C:20]([OH:26])=[O:19])=[CH:9][C:8](=[O:10])[C:6]=2[CH:7]=1
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).
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