Trifluoroacetic acid → 5-Amino-3-(trifluoromethyl)pyridine-2-carbonitrile

HRID 515780Notes

Reaction equation

HRID 515780 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]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 250200345-((4-Methoxybenzyl)amino)-3-(trifluoromethyl)picolinonitrile

Product 1

HCID 135322465-Amino-3-(trifluoromethyl)pyridine-2-carbonitrileYield 78.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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).

Workup

  1. customThe resulting reaction mixture
  2. customThe solvent and TFA were removed in vacuo and MeOH
  3. additionwas added to the residue
  4. filtrationwas filtered
  5. washwashed with MeOH
  6. customThe filtrate was evaporated to dryness
  7. customthe residue was partitioned between EtOAc
  8. washThe organic layer was washed two more times with a saturated aqueous sodium bicarbonate
  9. dry with materialdried over sodium sulfate
  10. customevaporated to dryness
  11. dissolutionThe residue was dissolved in DCM
  12. customprecipitated
  13. filtrationThis solid was filtered
  14. washwashed with hexanes

Sources & evidence

ORD record
ord-0cb34fe093454b8cb5696fc0ccd9169a
Source dataset
uspto-grants-2015_08
Patent number
US09108944B2

Reaction notes

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