Acetic Acid → Ethyl 6-{(E)-2-[3-(difluoromethoxy)-2-hydroxyphenyl]vinyl}imidazo[2,1-b][1,3]thiazole-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of Ethyl 6-{(E)-2-[2-(cyclopentyloxy)-3-(difluoromethoxy)phenyl]vinyl}imidazo[2,1-b][1,3]thiazole-5-carboxylate (4.10 g, 9.149 mmol) from Intermediate 5, Step 1 in a mixture of 48% hydrobromic acid (20 mL) and glacial acetic acid (20 mL) was heated at 60° C. for 2 h. The reaction mixture was cooled to room temperature and neutralized with saturated solution of NaHCO3. The mixture was extracted with ethyl acetate (2×100 mL) and the combined organic layers were washed with water (2×100 mL), dried over anhydrous Na2SO4. The residue obtained after the evaporation of the solvent was purified by silica gel column chromatography using 2% ethyl acetate in petroleum ether to obtain 3.0 g of the product as an off-white solid; 1H NMR (300 MHz, DMSO-d6) δ 1.40 (t, J=6.3 Hz, 3H), 4.34-4.43 (m, 2H), 6.80-6.90 (m, 1H), 7.05-7.10 (m, 1H), 7.12 (t, J=69.0 Hz, 1H), 7.40-7.48 (m, 2H), 7.78 (d, J=16.2 Hz, 1H), 7.87 (d, J=16.2 Hz, 1H), 8.10-8.16 (m, 1H), 9.79 (br s, 1H); APCI-MS (m/z) 381.15 (MH)+.

Provenance & Evidence