5-(Bromomethyl)-4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole

Synthesis

GENERAL STEPS: (4-methyl-2-(4-(trifluoromethyl)phenyl)thiazol-5-yl)methanol (15.0 g, 55.0 mmol) obtained in Example 2 was dissolved in anhydrous dichloromethane (300 mL). Triphenylphosphine (TPP, 5.7 g, 60.0 mmol, 1.1 eq.) and tetrabromomethane (20.0 g, 60.0 mmol, 1.1 eq.) were added sequentially to the mixture at room temperature. After 1 h of reaction, the solvent was removed by evaporation under reduced pressure. The residual triphenylphosphine oxide was precipitated with a mixture of hexane and ethyl acetate (v/v = 5/1), filtered and evaporated under reduced pressure to afford 5-(bromomethyl)-4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole (17.2 g, yield: 93%).1H-NMR (300 MHz, CDCl3): δ 8.00 (d, 2H, J = 8.1 Hz), 7.67 (d, 2H, J = 8.2 Hz), 4.72 (s, 2H), 2.47 (s, 3H).13C-NMR (78.5 MHz, CDCl3): δ 165.0, 153.8, 136.9, 132.4, 129.7 (q), 127.0, 126.3 (m), 122.5, 23.8. 15.5.

References

[1] Journal of Medicinal Chemistry, 2007, vol. 50, # 4, p. 685 - 695
[2] Patent: WO2003/106442, 2003, A1. Location in patent: Page 13
[3] Patent: WO2006/121223, 2006, A1. Location in patent: Page/Page column 15
[4] Patent: WO2003/106442, 2003, A1. Location in patent: Page 13-14