Trifluoroacetic acid → 5-Amino-3-(trifluoromethyl)pyridine-2-carbonitrile
Reaction equation
COC1C=CC(C[NH:8][C:9]2[CH:10]=[C:11]([C:17]([F:20])([F:19])[F:18])[C:12]([C:15]#[N:16])=[N:13][CH:14]=2)=CC=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:8][C:9]1[CH:10]=[C:11]([C:17]([F:20])([F:18])[F:19])[C:12]([C:15]#[N:16])=[N:13][CH:14]=1Participants
4
Procedure
5-((4-Methoxybenzyl)amino)-3-(trifluoromethyl)picolinonitrile (15 g, 49.02 mmol) was taken up in DCM (30 mL) and TFA (50 mL) was added. The resulting reaction mixture was stirred at room temperature for 3 h (until done by LC-MS). The solvent and TFA were removed in vacuo and MeOH was added to the residue. The beige solid that was not soluble in MeOH was filtered and washed with MeOH. The filtrate was evaporated to dryness and the residue was partitioned between EtOAc and a saturated solution of sodium bicarbonate. The organic layer was washed two more times with a saturated aqueous sodium bicarbonate, dried over sodium sulfate, and evaporated to dryness. The residue was dissolved in DCM and hexanes with swirling until a yellow solid precipitated. This solid was filtered and washed with hexanes to afford 7.2 g of 5-amino-3-(trifluoromethyl)picolinonitrile as a pale yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 8.17 (d, 1H), 7.28 (d, 1H), 6.99 (bs, 2H).