Methanol → 3-Fluoro-4-(3-methyl-1H-1,2,4-triazol-1-YL)aniline

HRID 475711Notes

Reaction equation

HRID 475711 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[CH:4][C:3]=1[N:11]1[C:15](C)=[N:14][CH:13]=[N:12]1.[CH3:17]O>[Pd]>[F:1][C:2]1[CH:7]=[C:6]([CH:5]=[CH:4][C:3]=1[N:11]1[CH:15]=[N:14][C:13]([CH3:17])=[N:12]1)[NH2:8]

Participants

4

Reactant 2

HCID 887MethanolHCID 584144611-(2-fluoro-4-nitrophenyl)-5-methyl-1H-1,2,4-triazole

Product 1

HCID 575269743-Fluoro-4-(3-methyl-1H-1,2,4-triazol-1-YL)anilineYield 93%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst2×

Procedure

10% Palladium on carbon (2.50 g, 23.5 mmol) was added under an atmosphere of nitrogen to a chilled (ice-water bath) solution of 1-(2-fluoro-4-nitrophenyl)-5-methyl-1H-1,2,4-triazole (15.0 g, 67.5 mmol, from preparation A, step1) dissolved in methanol (400 mL). The flask was repeatedly evacuated and flushed with hydrogen gas (double balloon). The resulting mixture was allowed to warm to rt and left to stir for 72 h under the hydrogen atmosphere. The vessel was subsequently purged with nitrogen gas. The reaction vessel and it contents were chilled (ice-water bath) and an additional portion of 10% Palladium on carbon (2.50 g, 23.5 mmol) was added. The flask was repeatedly evacuated and flushed with hydrogen gas (double balloon). The resulting mixture was allowed to warm to rt and left to stir for 6 h under the hydrogen atmosphere. The vessel was subsequently purged with nitrogen gas. The crude reaction mixture was filtered through a short plug of diatomaceous earth (Celite®). The reaction vessel and the Celite® were rinsed with fresh methanol. The combined filtrates were concentrated in vacuo. The residue was dried under high vacuum overnight to afford 3-fluoro-4-(3-methyl-1H-1,2,4-triazol-1-yl)aniline (12.1 g, 63.0 mmol, 93% yield) as a blackish/grey solid. LC-MS (M+H)+ 193.2. 1H NMR (500 MHz, CDCl3) δ ppm 8.31 (d, J=2.4 Hz, 1H), 7.47 (t, J=8.7 Hz, 1H), 6.47-6.58 (m, 2H), 3.97 (br. s., 2H), 2.48 (s, 3H).

Workup

  1. customThe flask was repeatedly evacuated
  2. customflushed with hydrogen gas (double balloon)
  3. waitleft
  4. customThe vessel was subsequently purged with nitrogen gas
  5. temperatureThe reaction vessel and it contents were chilled (ice-water bath)
  6. customThe flask was repeatedly evacuated
  7. customflushed with hydrogen gas (double balloon)
  8. temperatureto warm to rt
  9. waitleft
  10. stirringto stir for 6 h under the hydrogen atmosphere
  11. customThe vessel was subsequently purged with nitrogen gas
  12. customThe crude reaction mixture
  13. filtrationwas filtered through a short plug of diatomaceous earth (Celite®)
  14. washThe reaction vessel and the Celite® were rinsed with fresh methanol
  15. concentrationThe combined filtrates were concentrated in vacuo
  16. customThe residue was dried under high vacuum overnight

Sources & evidence

ORD record
ord-b6de073bf8764e95a45dfafe6ad41e09
Source dataset
uspto-grants-2014_01
Patent number
US08637525B2

Reaction notes

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