反应详情

A mixture of ethyl 4-amino-3-hydroxy-phenylacetate (3.3 g, Reference Example 2) and o-tolylisothiocyanate (2.5 mL) in ethanol (150 mL) was stirred at room temperature for about 2 hours. After standing at room temperature overnight the mixture was evaporated and the residue was subjected to flash chromatography on silica eluting with a mixture of pentane and ethyl acetate (7:3, v/v) to give a yellow foam. A solution of this material in ethanol (150 mL was treated with dicyclohexylcarbodiimide (3.0 g) and the mixture was heated at reflux temperature for 2 hours. The mixture was evaporated and the residue subjected to short column chromatography on silica eluting with a mixture of 5-10% tert-butyl methyl ether in dichloromethane to remove dicyclohexylurea. The resulting light yellow oil was dissolved in ethanol (100 mL) and the solution was treated with sodium hydroxide solution (15 mL, 1M) then heated at reflux temperature for 2 hours. The reaction mixture was evaporated and the residue was dissolved in water. The solution was washed with ethyl acetate and the aqueous layer was acidified to pH 1 by addition of concentrated hydrochloric acid. The resulting white precipitate was collected by filtration, then washed thoroughly with water, and then dried to give the title compound (1.8 g) as a white solid.

1. waitAfter standing at room temperature overnight
2. customthe mixture was evaporated
3. additionthe residue was subjected to flash chromatography on silica eluting with a mixture of pentane and ethyl acetate (7:3
4. customv/v) to give a yellow foam
5. temperaturethe mixture was heated
6. temperatureat reflux temperature for 2 hours
7. customThe mixture was evaporated
8. additionthe residue subjected to short column chromatography on silica eluting with a mixture of 5-10% tert-butyl methyl ether in dichloromethane
9. customto remove dicyclohexylurea
10. dissolutionThe resulting light yellow oil was dissolved in ethanol (100 mL)
11. additionthe solution was treated with sodium hydroxide solution (15 mL, 1M)
12. temperaturethen heated
13. temperatureat reflux temperature for 2 hours
14. customThe reaction mixture was evaporated
15. dissolutionthe residue was dissolved in water
16. washThe solution was washed with ethyl acetate
17. additionthe aqueous layer was acidified to pH 1 by addition of concentrated hydrochloric acid
18. filtrationThe resulting white precipitate was collected by filtration
19. washwashed thoroughly with water
20. customdried