Cyanoacetic acid hydrazide → 2-(3-(4-Fluorophenyl)-1H-1,2,4-triazol-5-yl)acetonitrile

HRID 1397319Notes

Reaction equation

HRID 1397319 reaction equation
[C:1]([CH2:3][C:4]([NH:6][NH2:7])=O)#[N:2].[OH-].[Na+].Cl.[F:11][C:12]1[CH:21]=[CH:20][C:15]([C:16](=[NH:19])OC)=[CH:14][CH:13]=1>CO.CCOC(C)=O>[F:11][C:12]1[CH:21]=[CH:20][C:15]([C:16]2[N:19]=[C:4]([CH2:3][C:1]#[N:2])[NH:6][N:7]=2)=[CH:14][CH:13]=1

Participants

6

Reactant 3

HCID 8820Cyanoacetic acid hydrazideHCID 14798Sodium HydroxideHCID 14685563Methyl 4-fluorobenzimidate hydrochloride

Product 1

HCID 508774582-(3-(4-Fluorophenyl)-1H-1,2,4-triazol-5-yl)acetonitrileYield 47%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-Cyanoacetohydrazide (172 mg, 1.74 mmol) and NaOH (66 mg, 1.66 mmol) were added to a solution of methyl 4-fluorobenzimidate hydrochloride (300 mg, 1.58 mmol) in dry MeOH (5 mL) and the mixture was heated to reflux for 1 h. The reaction mixture was concentrated under reduced pressure and the residue obtained was diluted with EtOAc. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica 60-120 mesh, eluant 20-25% EtOAc in petroleum ether) to yield 2-(3-(4-fluorophenyl)-1H-1,2,4-triazol-5-yl)acetonitrile (150 mg, yield 47%). 1H NMR (400 MHz, DMSO-d6) δ 8.04-7.99 (m, 2H), 7.39-7.33 (m, 2H), 4.11 (s, 2H). MS (ESI) m/z: Calculated for C10H7FN4: 202.07. found: 203.2 (M+H)+.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 1 h
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. customthe residue obtained
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by column chromatography (silica 60-120 mesh, eluant 20-25% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-9967a86419b043829dff89a5869a7e1a
Source dataset
uspto-grants-2014_12
Patent number
US08901156B2

Reaction notes

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