Hydrochloric Acid → 2-fluoro-4-(1H-1,2,4-triazol-1-yl)benzonitrile

HRID 1372245

Reaction equation

HRID 1372245 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6](CN)=[C:5]([N:11]2[CH:15]=[N:14][CH:13]=[N:12]2)[CH:4]=1.FC1C=CC([C:21]#[N:22])=C(N2C=NC=N2)C=1.Cl>C(O)C.[Pd]>[N:11]1([C:5]2[CH:6]=[CH:7][C:8]([C:21]#[N:22])=[C:3]([F:2])[CH:4]=2)[CH:15]=[N:14][CH:13]=[N:12]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 210698804-fluoro-2-(1H-1,2,4-triazol-1-yl)benzonitrileHCID 21069882(4-Fluoro-2-(1H-1,2,4-triazol-1-yl)phenyl)methanamine hydrochloride

Product 1

HCID 210698712-fluoro-4-(1H-1,2,4-triazol-1-yl)benzonitrileYield 99%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

(4-Fluoro-2-(1H-1,2,4-triazol-1-yl)phenyl)methanamine hydrochloride). Intermediate 67, 4-fluoro-2-(1H-1,2,4-triazol-1-yl)benzonitrile, (2.46 g, 13.13 mmol) was dissolved in hot ethanol (150 mL). To this was added 1N HCl (15 mL) followed by 10% Pd—C (200 mg). The mixture was treated with H2 at 55 psi for 4 h in a Parr shaker then filtered over Celite and the solvent removed under reduced pressure. The resulting residue was partitioned between ethyl acetate and water. The aqueous phase was separated and lyophilized to afford the title compound as a white powder (2.96 g, 99% yield). 1H NMR (500 MHz, CD3OD) δ ppm: 9.51 (1H, s), 8.63 (1H, s), 7.85 (1H, dd, J=8.5, 5.8 Hz), 7.68 (1H, dd, J=8.8, 2.4 Hz), 7.49 (1H, td, J=8.3, 2.4 Hz), 4.20 (2H, s). LCMS (M+H) calcd for C9H10N4F: 193.08. found: 193.16.

Workup

  1. additionThe mixture was treated with H2 at 55 psi for 4 h in a Parr shaker
  2. filtrationthen filtered over Celite
  3. customthe solvent removed under reduced pressure
  4. customThe resulting residue was partitioned between ethyl acetate and water
  5. customThe aqueous phase was separated

Sources & evidence

ORD record
ord-7c8b0a5a6d7c4b58b03b8dab16262f84
Source dataset
uspto-grants-2007_01
Patent number
US07157447B2

Linked notes

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