Water → Methyl 5-(2,2,2-trifluoroethoxy)pyridine-2-carboxylate

To a solution of methyl 5-hydroxypyridine-2-carboxylate (10.1 g, 65.95 mmol) and cesium carbonate (42.9 g, 131.9 mmol) in DMF (1 L) is added a solution of 2,2,2-trifluoroethyl trifluoromethanesulfonate (22.96 g, 98.93 mmol) in 20 ml of DMF over 2 hours. The reaction is stirred 4 hours at room temperature and then poured over water (1 L) and stirred for additional 1 hour. A brown solid is collected by filtration and washed with additional water. The solid is dried to a constant weight to give the intermediate compound (10.3 g 66%) of methyl 5-(2,2,2-trifluoroethoxyl)pyridine-2-carboxylate which is used without further purification. To a solution of methyl 5-(2,2,2-trifluoroethoxyl)pyridine-2-carboxylate (4.5 g, 19.1 mmol) in methanol (45 mL) is added sodium hydroxide 1 M solution (38.2 ml, 38.2 mmol) and the reaction is stirred for 2 hours at room temperature. The pH of the reaction mixture is adjusted with HCl 35% w/w to adjust pH=1 and then the resulting solid is isolated by filtration. The solid is washed with water and then dried under vacuum to give the title compound (3 g, 70%). ES/MS (m/z): 222.1 (M+1).

1. stirringstirred for additional 1 hour
2. filtrationA brown solid is collected by filtration
3. washwashed with additional water
4. customThe solid is dried to a constant weight

ORD record

ord-2f1d8a75cf1a4e97b57843968a12da8c

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09169271B2