Br[C:2]([F:9])([F:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4].C1COCC1.[CH2:15]([C:18]1[CH:25]=[CH:24][C:21]([CH:22]=[O:23])=[CH:20][CH:19]=1)[CH2:16][CH3:17].Cl>[Zn].C(OCC)(=O)C>[F:8][C:2]([F:9])([CH:22]([OH:23])[C:21]1[CH:24]=[CH:25][C:18]([CH2:15][CH2:16][CH3:17])=[CH:19][CH:20]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4]To a reaction vessel under a nitrogen atmosphere, 4.4 g of well-dried zinc, 10.3 g of ethyl bromodifluoroacetate (e-14) and 25 ml of THF were added, and the resultant mixture was cooled to 0° C. and stirred for 1 hour. The solution was slowly added dropwise in a temperature range of 20° C. to 25° C. to another reaction vessel under a nitrogen atmosphere in which 5.0 g of 4-propylbenzaldehyde (e-23) and 50 ml of THF were put, and the resultant mixture was further subjected to heating reflux for 4 hours. After cooling the resultant reaction mixture to 25° C., 200 ml of 1 N HCl aqueous solution and 200 ml of ethyl acetate were added to separate the mixture into an organic layer and an aqueous layer, and an extraction operation was performed. The resultant organic layer was isolated, and washed with water, a saturated aqueous solution of sodium hydrogencarbonate and water, and then the resultant solution was dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure, the resultant residue was purified by a preparative isolation operation by means of column chromatography using a mixed solvent of heptane and ethyl acetate (heptane:ethyl acetate=20:1 in a volume ratio) as an eluent and silica gel as a filler, the resultant product was dried, and thus 9.0 g of ethyl 2,2-difluoro-3-hydroxy-3-(4-propylphenyl)propanoate (e-24) was obtained. A yield based on compound (e-23) was 97.8%.
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