反应详情

温度

110 °C

2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazole a2 (10 g, 42.16 mmol, 1 eq), formaldehyde (16 g, 421.6 mmol, 10 eq) and hydrochloric acid (37%, 8.2 ml, 2 eq) are diluted in sulfolane (250 ml). The reaction mixture is heated at 110° C. overnight. Water (500 ml) is added and the mixture is heated at 50° C. for 2 h. The solvent is then removed under reduced pressure. The residue is purified by chromatography over silicagel (gradient; eluent: CH2Cl2/MeOH/NH4OH from 100/0/0 to 99/1/0.1) to afford 6.5 g of [2-(methoxymethyl)-6-(trifluoromethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methanol a3 as a yellow solid.

1. temperaturethe mixture is heated at 50° C. for 2 h
2. customThe solvent is then removed under reduced pressure
3. customThe residue is purified by chromatography over silicagel (gradient; eluent: CH2Cl2/MeOH/NH4OH from 100/0/0 to 99/1/0.1)