Synthesis
General procedure for the synthesis of 2-amino-4-trifluoromethylthiazole from 3-bromo-1,1,1-trifluoroacetone and thiourea: Thiourea (4.0 g, 52.3 mmol) and 3-bromo-1,1,1-trifluoropropan-2-one (5.5 mL, 10 g, 52.3 mmol) were added to ethanol (100 mL) and the reaction was heated for 2 hours at 50 °C. After completion of the reaction, it was cooled to room temperature and the reaction solution was concentrated to dryness. The residue was dissolved in water and the pH was adjusted with 2 M NaOH solution to >12. Subsequently, four extractions were performed with ether. The organic extracts were combined, dried with sodium sulfate, filtered and concentrated in vacuum. The resulting crude product was purified by silica gel column chromatography (CH2Cl2 as eluent) to afford 2-amino-4-trifluoromethylthiazole (6.9 g, 79% yield). es/MS m/z 169 (M + 1)+.
References
[1] Patent: WO2008/36579, 2008, A1. Location in patent: Page/Page column 43
[2] Journal of Heterocyclic Chemistry, 1991, vol. 28, # 4, p. 907 - 911
[3] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1988, vol. 27, # 1-12, p. 1051 - 1053
[4] Journal of Organic Chemistry, 1955, vol. 20, p. 499,505
[5] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1981, p. 2335 - 2339
