4-AMINO-2-(TRIFLUOROMETHYL)NICOTINIC ACID synthesis

Yield:1018678-42-6 95%

Reaction Conditions:

Stage #1: methyl 4-amino-2-(trifluoromethyl)nicotinatewith methanol;lithium hydroxide;water in 1,4-dioxane at 85; for 8 h;
Stage #2: with hydrogenchloride;water in 1,4-dioxane;methanol;

Steps:

Preparation of 4-Amino-2-(trifluoromethyl)nicotinic acid To a stirred solution of methyl 4-amino-2-(trifluoromethyl)nicotinate (1.97 g, 8.97 mmol) in dioxane/methanol/water (3:2:1 ratio by volume) is added lithium hydroxide (0.365 g, 15.2 mmol). The mixture was heated at 85° C. for 8 hours. The reaction mixture was cooled to room temperature and conc. HCl was added dropwise to adjust the pH to 2-3. Saturated NaCl solution was added. The aqueous layer is extracted with ethyl acetate (12*). The organic layer is washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to afford 1.75 g (95%) of 4-amino-2-(trifluoromethyl)nicotinic acid as a yellow solid. ¹H NMR (400 MHz, CD₃OD), 8.09 (d, 1H), 6.93 (d, 1H), LC/MS (M+1)=207.1.

References:

US2008/85887,2008,A1 Location in patent:Page/Page column 19