2-(bromomethyl)-4-phenylthiazole

Synthesis

General procedure for the synthesis of 2-bromomethyl-4-phenylthiazole from 4-phenyl-2-hydroxymethylthiazole: (4-phenylthiazol-2-yl)methanol (Example 4C, 0.530 g, 2.77 mmol) was dissolved in dichloromethane (10 mL) and cooled to 0°C (ice bath). Phosphorus tribromide (0.118 mL, 1.247 mmol) was added dropwise over 2 min, and a thick white gel formed immediately.After 10 min, the ice bath was removed and the reaction mixture was stirred for 4 h at 22°C. Upon completion of the reaction, the reaction was quenched with ice (~10 g) and the mixture was poured into a mixture of ethyl acetate (150 mL) and saturated sodium bicarbonate solution (50 mL). The organic phase was separated, washed with brine, dried over anhydrous magnesium sulfate and subsequently concentrated under vacuum. The solid residue obtained was purified by silica gel column chromatography (2.5 x 6 cm, toluene as eluent) to afford the target product 2-bromomethyl-4-phenylthiazole (0.561 g, 80% yield) as a light yellow oil, which solidified to a light yellow solid in the refrigerator.LC (Method C): retention time 2.062 min.HRMS (ESI) calculated value C10H9BrSNa [M+Na]+ m/z 253.9634, measured value 253.9655. 1H NMR (CDCl3, 400 MHz) δ ppm: 4.81 (s, 2H), 7.34-7.39 (m, 1H), 7.41-7.47 (m, 2H), 7.52 (s, 1H), 7.86-7.92 (m , 2H).

References

[1] Patent: WO2013/163279, 2013, A1. Location in patent: Paragraph 00150
[2] Acta Chemica Scandinavica (1947-1973), 1953, vol. 7, p. 885,887
[3] Journal of the American Chemical Society, 1931, vol. 53, p. 1470,1472
[4] Patent: US2013/289238, 2013, A1. Location in patent: Page/Page column