Synthesis
Step 1: Synthesis of ethyl 2-amino-4-trifluoromethylthiazole-5-carboxylate (A-31)
To an ethanol (200 mL) suspension of thiourea (3.3 g, 22.88 mmol) was added ethyl 2-chloro-4,4,4-trifluoroacetoacetate (5 g, 22.88 mmol), and the resulting reaction mixture was heated at 80 °C for 24 hours. Subsequently, the reaction mixture was cooled to room temperature and concentrated under vacuum. The crude product was purified by column chromatography to afford ethyl 2-amino-4-trifluoromethylthiazole-5-carboxylate (A-31) as a colorless oil (5.98 g, 85% yield).
1H NMR (500 MHz, CDCl3) δ 4.32 (q, 2H, J = 7.0 Hz), 3.56 (m, 4H), 1.70 (m, 6H), 1.36 (t, 3H, J = 7.0 Hz); LCMS (ESI) [M + 1]+ 309.3.
References
[1] Journal of Heterocyclic Chemistry, 2017, vol. 54, # 6, p. 3395 - 3402
[2] Journal of Heterocyclic Chemistry, 2017, vol. 54, # 2, p. 1625 - 1629
[3] Patent: WO2010/59606, 2010, A2. Location in patent: Page/Page column 169
[4] Tetrahedron Letters, 2005, vol. 46, # 13, p. 2251 - 2252
[5] Patent: US2004/138268, 2004, A1. Location in patent: Page/Page column 15
