Chloroacetaldehyde → 2-Bromoimidazo[2,1-b][1,3,4]thiadiazole

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Reaction Steps

To a suspension of 5-bromo-1,3,4-thiadiazol-2-amine (60 g, 0.33 mol) in H2O (1.5 L), a solution of chloroacetaldehyde (50% wt in water, 64.5 mL, 0.50 mol) was added, and the mixture was stirred at reflux temperature for 5 h. A second portion of chloroacetaldehyde (20.6 mL, 0.5 eq) was added, and stirring was continued overnight. The starting material had been consumed completely, and the reaction mixture was cooled to RT. The solid was removed by filtration and washed with water. The mother liquor was neutralized with a sat. aq. solution of NaHCO3 and extracted with DCM (2×1 L). The organic layers were washed with brine (2×600 mL), dried and evaporated in vacuo. The brown residue obtained was triturated with a mixture of MeOH and MTBE (1:1, 70 mL) to afford the desired product as a pale yellow solid. The mother liquors were purified by chromatography (SiO2, DCM) to yield some more product. Combined yield: 9.4 g (14%). MS (ESI+): m/z=204 [M+H]+; 1H-NMR(CDCl3): 7.36 (d, 1H); 7.56 (d, 1H).

Provenance & Evidence