反应详情

O-methylisourea hydrogensulfate (3.44 g, 20 mmol) was added to a solution of 3-(3,5-di-tert-butyl-4-hydroxy-phenyl)-3-oxo-2-(dimethylamino)methylene]-propanoic acid methyl amide (3.55 g, 9.84 mmol) in 2-propanol (37.5 mL). The suspension was stirred at room temperature for 10 min then a 1 M solution of potassium tert. butoxide in tert. butanol (37.5 mL) was added and the mixture was immersed into a bath maintained at 80° C. and stirred for 4 hours. The reaction mixture was allowed to cool to ambient temperature and was then distributed between dichloromethane (150 mL) and water (75 mL). The organic layer was washed with water (2×50 mL), once with brine (10 mL), dried over magnesium sulfate and evaporated. The residue obtained was dissolved in dichloromethane and flash-chromatographed using DCM, 1:19, 1:9, and 1:3 ethyl acetate-dichloromethane, followed by ethyl acetate as mobile phases. Early fraction eluted 3-(3,5-di-tert-butyl-4-hydroxy-phenyl)-3-oxo-propanoic acid methyl amide, which is the solvolysis product of the starting material; the title compound was eluted using 1:3 ethyl acetate-dichloromethane. The fractions containing the product were evaporated; the residue redissolved in hot DCM, diluted with cyclohexane then heated to remove some DCM and allowed to crystallize. The solids obtained were redissolved in ethyl acetate, the solution filtered, concentrated, diluted with cyclohexane and allowed to crystallize to give white crystals. The solids were filtered off, washed with cyclohexane and hexane, and dried to constant weight at 55° C. and 20 torr to afford 1.20 g of the title compound (32.8% yield). TLC (ethyl acetate), Rf 0.68, 1H-NMR (300 MHz, DMSO-d6) δ 1.40 (9H, s), 2.75 (3H, d, J=3.9 Hz), 3.98 (3H, s), 7.55 (1H, s), 7.69 (2H, s), 8.44 (1H br s), 8.49 (1H, s).

1. customthe mixture was immersed into a bath
2. temperaturemaintained at 80° C.
3. stirringstirred for 4 hours
4. temperatureto cool to ambient temperature
5. washThe organic layer was washed with water (2×50 mL), once with brine (10 mL)
6. dry with materialdried over magnesium sulfate
7. customevaporated
8. customThe residue obtained
9. customflash-chromatographed
10. washEarly fraction eluted 3-(3,5-di-tert-butyl-4-hydroxy-phenyl)-3-oxo-propanoic acid methyl amide, which
11. washthe title compound was eluted
12. additionThe fractions containing the product
13. customwere evaporated
14. dissolutionthe residue redissolved in hot DCM
15. additiondiluted with cyclohexane
16. temperaturethen heated
17. customto remove some DCM
18. customto crystallize
19. customThe solids obtained
20. filtrationthe solution filtered
21. concentrationconcentrated
22. additiondiluted with cyclohexane
23. customto crystallize
24. customto give white crystals
25. filtrationThe solids were filtered off
26. washwashed with cyclohexane and hexane
27. customdried to constant weight at 55° C.