Trifluoroacetic acid → 2-[4-(2-Aminoethyl)-phenoxy]-isonicotinonitrile

HRID 1409291Notes

Reaction equation

HRID 1409291 reaction equation
C(OC(=O)[NH:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]2[CH:22]=[C:21]([C:23]#[N:24])[CH:20]=[CH:19][N:18]=2)=[CH:12][CH:11]=1)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]2[CH:22]=[C:21]([CH:20]=[CH:19][N:18]=2)[C:23]#[N:24])=[CH:12][CH:11]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59730249{2-[4-(4-Cyanopyridin-2-yloxy)phenyl]ethyl}carbamic acid tert-butyl ester

Product 1

HCID 597302792-[4-(2-Aminoethyl)-phenoxy]-isonicotinonitrileYield 179.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

{2-[4-(4-Cyanopyridin-2-yloxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester (5.57 g, 8.2 mmol) was dissolved with magnetic stirring in CH2Cl2 (100 mL) in a 250 mL round bottom flask equipped with a dry nitrogen line at 25° C. To this solution was added trifluoroacetic acid (10 mL), and the reaction mixture was kept at 25° C. for 3 h. The solution was concentrated in vacuo. The residue was taken up in H2O (50 mL) and EtOAc (75 mL) and treated with conc. ammonium hydroxide (NH4OH) to adjust the pH to 9-10. The layers were separated, and the aqueous fraction was extracted twice with EtOAc. The pooled organic fractions were filtered and concentrated in vacuo to afford 2-[4-(2-aminoethyl)-phenoxy]-isonicotinonitrile (3.52 g, 89%) as a beige waxy solid: 1H NMR (400 MHz, CDCl3) δ 8.32 (d, J=5.1 Hz, 1H), 7.27 (m, 2H), 7.19 (d, J=5.1 Hz, 1H), 7.15 (s, 1H), 7.07 (d, J=8.4 Hz, 2H), 3.00 (t, J=6.9 Hz, 2H), 2.78 (t, J=6.9 Hz, 2H), 1.63 (s, 2H); ESIMS m/z 240.1 ([M+H]+).

Workup

  1. customequipped with a dry nitrogen line at 25° C
  2. concentrationThe solution was concentrated in vacuo
  3. additionEtOAc (75 mL) and treated with conc. ammonium hydroxide (NH4OH)
  4. customThe layers were separated
  5. extractionthe aqueous fraction was extracted twice with EtOAc
  6. filtrationThe pooled organic fractions were filtered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-80259f28537f4ffb993bfd79d91cbd30
Source dataset
uspto-grants-2014_12
Patent number
US08921382B2

Reaction notes

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