反应详情

In a nitrogen atmosphere 5-thiocyanato-thiazol-2-ylamine (10 g, 64 mmol) dissolved in MeOH (300 mL) was added 2,3-dihydroxy-1,4-dithiolbutane (DTT, 9.8 g, 64 mmol) and stirred at room temperature for 1½ h. Then 2-bromo-2-methyl-propionic acid ethyl ester (13.6 g, 70 mmol) and K2CO3 (10.5 g, 76 mmol) was added and the reaction mixture was stirred for further 13 h. Addition of water (500 mL) and EtOAc (500 mL). Separation of the organic phase followed by extraction of the aqueous phase with EtOAc (2×300 mL). The combined organic phases were washed with water (500 mL) and brine (2×400 mL) and dried (MgSO4), filtered and evaporated. The crude product was dissolved in a small amount of DCM and purified by flash chromathography (heptane/EtOAc 2:1->1:2). Fractions containing the product were pooled and evaporated to a product containing impurities of DDT. This product was dissolved in diethyl ether (100 mL) and washed with water several times. The ether phase was dried (MgSO4), filtered and evaporated to give 8.45 g (54%) of 95% pure 2-(2-aminothiazol-5-ylsulfanyl)-2-methyl-propionic acid ethyl ester as light brown crystals.

1. stirringthe reaction mixture was stirred for further 13 h
2. customSeparation of the organic phase
3. extractionfollowed by extraction of the aqueous phase with EtOAc (2×300 mL)
4. washThe combined organic phases were washed with water (500 mL) and brine (2×400 mL)
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. customevaporated
8. dissolutionThe crude product was dissolved in a small amount of DCM
9. custompurified by flash chromathography (heptane/EtOAc 2:1->1:2)
10. additionFractions containing the product
11. customevaporated to a product
12. additioncontaining impurities of DDT
13. dissolutionThis product was dissolved in diethyl ether (100 mL)
14. washwashed with water several times
15. dry with materialThe ether phase was dried (MgSO4)
16. filtrationfiltered
17. customevaporated