反应详情

温度

0 °C

To 100 ml of a concentrated hydrochloric acid solution containing 19.3 g of 4-aminothiazole-5-carboxylic acid ethyl ester, 12 ml of an aqueous solution of 8.5 g of sodium nitrite was added dropwise at 0 to 5° C. This mixture was stirred at 0° C. for 30 minutes, and then 120 ml of a concentrated hydrochloric acid solution containing 84.9 g of stannous chloride was added dropwise thereto at 0 to 10° C. The mixture was further stirred at the same temperature for 2 hours and then stirred at room temperature for 30 minutes. The reaction mixture was filtered, and the filtrate was carefully added to 2 liters of an ethyl acetate suspension containing 500 g of potassium carbonate and 100 g of celite with stirring. Further, the filtered substance was added to this ethyl acetate suspension, and then the suspension was made basic with 150 ml of a 5 N sodium hydroxide aqueous solution. The mixture was allowed to stand, and then most of the supernatant (organic layer A: 1.5 liters) was collected. The remaining suspension was filtered through celite, and the celite was washed with 1 liter of ethyl acetate and 500 ml of water. The filtrate was separated into organic layer B and aqueous layer A. Ethyl acetate (1 liter) and anhydrous magnesium sulfate were added to the filtered substance, and the mixture was stirred and then filtered. Aqueous layer A was re-extracted with the resulting filtrate. Washing of the filtered substance and re-extraction of aqueous layer A were repeated 4 times in the same manner. Organic layer A and organic layer B were combined with the obtained organic layers, and the mixture was dried over anhydrous magnesium sulfate. The desiccating agent was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate-methanol) to give the title compound (11.9 g) as a light yellow solid.

1. additionwas added dropwise at 0 to 5° C
2. additionwas added dropwise
3. customat 0 to 10° C
4. stirringThe mixture was further stirred at the same temperature for 2 hours
5. stirringstirred at room temperature for 30 minutes
6. filtrationThe reaction mixture was filtered
7. additionthe filtrate was carefully added to 2 liters of an ethyl acetate suspension
8. additioncontaining 500 g of potassium carbonate and 100 g of celite
9. stirringwith stirring
10. additionFurther, the filtered substance was added to this ethyl acetate suspension
11. custommost of the supernatant (organic layer A: 1.5 liters) was collected
12. filtrationThe remaining suspension was filtered through celite
13. washthe celite was washed with 1 liter of ethyl acetate and 500 ml of water
14. customThe filtrate was separated into organic layer B and aqueous layer A
15. additionEthyl acetate (1 liter) and anhydrous magnesium sulfate were added to the filtered substance
16. stirringthe mixture was stirred
17. filtrationfiltered
18. extractionAqueous layer A was re-extracted with the resulting filtrate
19. washWashing of the filtered substance and re-extraction of aqueous layer A
20. dry with materialthe mixture was dried over anhydrous magnesium sulfate
21. customThe desiccating agent was removed by filtration
22. concentrationthe filtrate was concentrated under reduced pressure
23. customThe residue was purified by silica gel column chromatography (ethyl acetate-methanol)