[CH:1]([NH:3][CH2:4][C:5]1[S:6][CH:7]=[CH:8][N:9]=1)=[O:2].O.O.P([O-])(O)(O)=O.[Na+].[Br-:18].[Na+].BrBr.[OH-].[Na+].S([O-])([O-])=O.[Na+].[Na+]>O.O1CCCC1>[Br:18][C:7]1[S:6][C:5]([CH2:4][NH:3][CH:1]=[O:2])=[N:9][CH:8]=12-Formylaminomethylthiazole (200 g) was added to a solution of 4.5 kg of sodium dihydrogenphosphate dihydrate in 6 L of water, and the mixture was stirred at 30° C. Sodium bromide (4.0 kg) and 2 L of tetrahydrofuran were added thereto in that order. Bromine (1.49 kg) was added while adjusting the solution to pH 3 by the addition of a 6 N aqueous sodium hydroxide solution, and the mixture was stirred for 2 hr. The reaction mixture was added to a solution of 500 g of sodium sulfite in 4 L of water to stop the reaction and was then adjusted to pH 4.9 by the addition of a 6 N aqueous sodium hydroxide solution while maintaining the temperature of the mixture at 30° C. The reaction mixture was extracted with 10 L of ethyl acetate and then with 5 L of ethyl acetate. The organic layers were combined and were dried over anhydrous magnesium sulfate. The solvent was removed to bring the volume to 1 L, and the concentrate was stirred at 6° C. for 12 hr for crystallization to give 104.4 g of 5-bromo-2-formylaminomethylthiazole. The results of NMR analysis were in agreement with the results of analysis in Example 3.
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