Ethanol → Ethyl 2-methyl-1,3-thiazole-4-carboxylate

Thioacetamide (7.6 g, 100 mmol) was added to ethanol (60 mL), and the resultant suspension was cooled to 0° C. and treated with ethyl bromopyruvate (12.5 mL, 100 mmol). The resultant solution was stirred for five minutes at 0° C. at which time the ice bath was removed and the solution was allowed to warm to ambient temperature. After 0.5 h at ambient temperature, the solution was heated to reflux. After 12 h, the solvents were removed in vacuo, and the resultant crude product was taken up in ethyl acetate (300 mL). The organic phase was washed with saturated aqueous NaHCO3 (50 mL), and the basic aqueous solution was then extracted with additionalethyl acetate (2×50 mL). The combined organic solutions were washed with brine (50 mL), dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo to afford a yellow waxy solid. The crude product was dissolved in a small amount of hot ethyl acetate, diluted with hot hexane, and the resultant solution was allowed to cool to ambient temperature, seeded with a small amount of crude product, and transferred to the freezer. After 16 h the crystalline product was collected, washed with cold 8:1 hexane:ethyl acetate, and allowed to dry under high vacuum to afford ethyl 2-methyl-1,3-thiazole-4-carboxylate (11.76 g, 69% yield) as large brownish crystals. M.p. 56–58.5° C. 1H NMR (CDCl3, 300 MHz) δ 8.06 (s, 1H), 4.43 (q, 2H), 2.78 (s, 3H), 1.42 (t, 3H). MS (EI ionization) 171 (M+).

1. customwas removed
2. temperaturethe solution was heated to reflux
3. waitAfter 12 h
4. customthe solvents were removed in vacuo
5. washThe organic phase was washed with saturated aqueous NaHCO3 (50 mL)
6. extractionthe basic aqueous solution was then extracted with additionalethyl acetate (2×50 mL)
7. washThe combined organic solutions were washed with brine (50 mL)
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationThe filtrate was concentrated in vacuo
11. customto afford a yellow waxy solid
12. temperatureto cool to ambient temperature
13. customAfter 16 h the crystalline product was collected
14. washwashed with cold 8:1 hexane
15. customto dry under high vacuum

ORD record

ord-7dc1910f430448c4840133519ad1581a

Source dataset

uspto-grants-2005_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06956049B1