[F:1][C:2]1([F:16])[CH2:5][CH:4]([C:6]([O:8]CC2C=CC=CC=2)=O)[CH2:3]1.[CH3:17][C:18]1([CH3:26])[O:25][C:23](=[O:24])[CH2:22][C:20](=[O:21])[O:19]1.CCN=C=NCCCN(C)C.O>CO.CN(C1C=CN=CC=1)C.[Pd]>[F:16][C:2]1([F:1])[CH2:3][CH:4]([C:6]([CH:22]2[C:23](=[O:24])[O:25][C:18]([CH3:26])([CH3:17])[O:19][C:20]2=[O:21])=[O:8])[CH2:5]1
A mixture of benzyl 3,3-difluorocyclobutanecarboxylate (28 g, 0.12 mol) and Pd/C (5 g) in methanol (150 mL) was hydrogenated for 2 h at ambient temperature. Pd/C was filtered off and the filtrate was concentrated. The residue was dissolved in dichloromethane (200 mL) and cooled to 0° C. DMAP (30.8 g, 0.250 mol), Meldrum's acid (19.6 g, 0.140 mol) and EDCI (26.9 g, 0.140 mol) were added successively. The reaction mixture was stirred overnight at ambient temperature. Water (200 mL) was added and the resulting mixture was extracted with dichloromethane (300 mL×3). The organic extracts were combined, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel (dichloromethane/methanol=100:1 to 20:1) to afford 5-(3,3-difluorocyclobutanecarbonyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (24 g, 74% yield).
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