Potassium Carbonate → Ethyl 2-[(2-amino-1,3-thiazol-5-yl)sulfanyl]-2-methylpropanoate

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 11/2 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 16 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.1 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 (ca 14 g) containing impurities of DDT. The crude product was dissolved in diethyl ether (100 mL) and washed with water eight times. The ether phase was dried (MgSO4), filtered and evaporated to give 8.45 g (54%) of 95% pure 2-(2-amino-thiazol-5-ylsulfanyl)-2-methyl-propionic acid ethyl ester as light brown crystals. 1 As the DTT impurities is not easily removed by flash chromathography it's recommended that the crude product is dissolved in Et2O and subsequently washed with water several times at then purified by flash chromathography.

1. stirringthe reaction mixture was stirred for further 16 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. dissolutionevaporated.1 The crude product was dissolved in a small amount of DCM
8. custompurified by flash chromathography (heptane/EtOAc 2:1→1:2)
9. additionFractions containing the product
10. customevaporated to a product (ca 14 g)
11. additioncontaining impurities of DDT
12. dissolutionThe crude product was dissolved in diethyl ether (100 mL)
13. washwashed with water eight times
14. dry with materialThe ether phase was dried (MgSO4)
15. filtrationfiltered
16. customevaporated

ORD record

ord-91b2f5292e9b4fa486260f22b7b8ce76

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08586614B2