Lithium Hydroxide → 2-Fluoro-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzoic acid

Participants

Reaction Steps

Prepared using General Procedures 6 and 9. To a stirring solution of 2-(4-methoxy-2-(trifluoromethyl)phenyl)acetic acid (500 mg, 2.13 mmol) and methyl 4-amino-2-fluorobenzoate (361 mg, 2.13 mmol) in DMF (5 mL) were added HATU (852 mg, 2.24 mmol) and TEA (744 μl, 5.34 mmol). After stirring at room temperature for 18 h the reaction mixture was diluted with EA (20 mL) and washed with NaHCO3 (2×20 mL) and 1 M HCl (2×20 mL). The organic phase was concentrated in vacuo to afford an orange solid which was dissolved in THF (5 mL) and MeOH (2 mL) and 1 M LiOH (4.3 μL, 4.27 mmol) was added. After stirring at room temperature for 2 h the reaction mixture was concentrated in vacuo, the residue dissolved in water (10 mL) and acidified to pH 1 using 1 M HCl. A white precipitate was formed and the mixture was filtered under vacuum. The captured solid was washed with MeOH (5 mL) to afford a pale brown solid. The solid was triturated with MeOH (5 mL) to afford 198 mg (25%) of 2-fluoro-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzoic acid INT-78 as a white solid. LCMS-ESI (m/z) calculated for C17H13F4NO4: 371; found 372 [M+H]+, tR=1.94 min (Method 10).

Provenance & Evidence