S(Cl)([Cl:3])=O.[OH:5][C:6]1[C:11](=[O:12])[CH:10]=[C:9]([CH:13]([OH:18])[C:14]([F:17])([F:16])[F:15])[N:8]([CH3:19])[C:7]=1[CH2:20]O.CO.[Cl:24]CCl>C(#N)C>[ClH:3].[Cl:24][CH2:20][C:7]1[N:8]([CH3:19])[C:9]([CH:13]([OH:18])[C:14]([F:17])([F:16])[F:15])=[CH:10][C:11](=[O:12])[C:6]=1[OH:5]Thionyl chloride (0.48 mL, 6.6 mmol) was added dropwise to a suspension of 3-hydroxy-2-(hydroxymethyl)-1-methyl-6-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-4(1H)-one (1.50 g, 5.9 mmol) in acetonitrile (45 mL). The progress of the reaction was monitored by TLC (eluant: methanol:dichloromethane, 15:100, v:v), and the starting material was consumed within 5 min. The reaction mixture was concentrated repeatedly in acetonitrile to give a solid, which was then washed with acetonitrile (15 mL×1). Thus, 2-(chloromethyl)-3-hydroxy-1-methyl-6-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-4(1H)-one hydrochloride was obtained as a white solid (1.18 g).
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