Ethyl bromopyruvate → Ethyl 2-(trifluoromethyl)-1,3-thiazole-4-carboxylate

A mixture of 2,2,2-trifluoroacetamide (7.12 g, 63 mmol) and Lawesson's reagent (15.3 g, 37.8 mmol) in THF (60 mL) was heated at reflux for 18 hours. The reaction was then cooled down to RT and treated with ethyl bromopyruvate (8.0 mL, 63 mmol). The reaction was stirred at reflux for an additional 18 hours, then concentrated under vacuum and diluted with ethyl acetate. This mixture was washed with water (1×) and brine (1×), dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (8×11 cm, toluene, then second time with 120 g silica gel, hexane/ethyl acetate) to give the title material (4.47 g, 32%) as a pale yellow solid. 1H NMR (CDCl3, 400 MHz) δ 8.37 (s, 1H), 4.45 (q, J=7.0 Hz, 2H), 1.41 (t, J=7.0 Hz, 1H).

1. temperaturewas heated
2. temperatureat reflux for 18 hours
3. temperatureat reflux for an additional 18 hours
4. concentrationconcentrated under vacuum
5. additiondiluted with ethyl acetate
6. washThis mixture was washed with water (1×) and brine (1×)
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was purified by silica gel chromatography (8×11 cm, toluene

ORD record

ord-009e8501044f409db673bc005f1e1143

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09303065B2