Ammonium Chloride → (3-Amino-6-fluoro-2-phenylaminophenyl)acetonitrile

HRID 243243Notes

Reaction equation

HRID 243243 reaction equation
[F:1][C:2]1[C:7]([CH2:8][C:9]#[N:10])=[C:6]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:5]([N+:18]([O-])=O)=[CH:4][CH:3]=1.[Cl-].[NH4+]>CO.O.[Fe]>[NH2:18][C:5]1[C:6]([NH:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[C:7]([CH2:8][C:9]#[N:10])[C:2]([F:1])=[CH:3][CH:4]=1

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 68157927(6-Fluoro-3-nitro-2-phenylaminophenyl)acetonitrile

Product 1

HCID 68158122(3-Amino-6-fluoro-2-phenylaminophenyl)acetonitrileYield 55.6%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

(6-Fluoro-3-nitro-2-phenylaminophenyl)acetonitrile (463 mg, 1.70 mmol), iron powder (194 mg, 3.41 mmol), and ammonium chloride (263 mg, 5.12 mmol) in methanol (10 mL) and water (3 mL) were heated at 90° C. for 1 h. The reaction mixture was filtered and the filtrate concentrated in vacuo. The residue was dissolved in water and extracted with EtOAc (3×20 mL). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, eluting with 0-100% EtOAc in cyclohexane) to yield the title compound as brown solid (228 mg, 55%). 1H NMR 400 MHz δ (CDCl3): 7.23-7.17 (2H, m), 6.95 (1H, t, J=8.9 Hz), 6.83 (1H, tt, J=7.4, 1.0 Hz), 6.77 (1H, dd, J=8.9, 5.5 Hz), 6.61-6.56 (2H, m), 5.12 (1H, br s), 3.79 (2H, br s), 3.59 (2H, d, J=1.2 Hz).

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationthe filtrate concentrated in vacuo
  3. dissolutionThe residue was dissolved in water
  4. extractionextracted with EtOAc (3×20 mL)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. washThe resultant residue was subjected to flash chromatography (SiO2, eluting with 0-100% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-729ed495ffc445909e40f59a472847b6
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

Loading…