[Cl:1][C:2]1[C:8]([O:9][CH2:10][C:11]([O:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[O:12])=[CH:7][C:5]([NH2:6])=[C:4]([F:19])[CH:3]=1.[C:20]1(=O)[O:25][C:23](=[O:24])[C:22]2[CH2:26][CH2:27][CH2:28][CH2:29][C:21]1=2.C(O)(=O)CC.C1(C)C=CC=CC=1>N1CCCCC1.O>[Cl:1][C:2]1[C:8]([O:9][CH2:10][C:11]([O:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[O:12])=[CH:7][C:5]([N:6]2[C:23](=[O:24])[C:22]3[CH2:26][CH2:27][CH2:28][CH2:29][C:21]=3[C:20]2=[O:25])=[C:4]([F:19])[CH:3]=1A mixture of the compound (II) (12.0 g), 3,4,5,6-tetrahydrophthalic anhydride (7.56 g), piperidine (0.18 g), propionic acid (0.30 g) and toluene (24 g) was heated under reflux for 5 hours, during which water as by-produced was azeotropically removed. To the reaction mixture, toluene (24 g) and water (24 g) were added, and the organic layer was separated and concentrated under reduced pressure. To the residue, water (18 g) and methanol (33 g) were added, and the precipitated crystals were collected by filtration to give N-[4-chloro-2-fluoro-5-(pentyloxycarbonylmethyloxy)-phenyl]-3,4,5,6-tetrahydrophthalimide (Compound (I)) (16.1 g). By the use of a high speed liquid chromatography, the purity of the compound (I) as the major product and the amount of the by-produced 4-chloro-2-fluoro-5-(pentyloxycarbonylmethyloxy)acetanilide (hereinafter referred to as "N-acetyl compound") as a contaminant were determined according to the inner standard method and the area comparison method, respectively.
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