Ammonium Chloride → (5-Amino-2-methyl-phenyl)-[2-chloro-4-(2,4-difluoro-phenylamino)-phenyl]-methanone

HRID 1012610

Reaction equation

HRID 1012610 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=2[F:16])[CH:5]=[CH:4][C:3]=1[C:17]([C:19]1[CH:24]=[C:23]([N+:25]([O-])=O)[CH:22]=[CH:21][C:20]=1[CH3:28])=[O:18].[NH4+].[Cl-]>CO.[Zn]>[NH2:25][C:23]1[CH:22]=[CH:21][C:20]([CH3:28])=[C:19]([C:17]([C:3]2[CH:4]=[CH:5][C:6]([NH:8][C:9]3[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=3[F:16])=[CH:7][C:2]=2[Cl:1])=[O:18])[CH:24]=1

Participants

5

Reactant 2

HCID 25517Ammonium ChlorideHCID 11618303[2-Chloro-4-(2,4-difluoro-phenylamino)-phenyl]-(2-methyl-5-nitro-phenyl)-methanone

Product 1

HCID 11538012(5-Amino-2-methyl-phenyl)-[2-chloro-4-(2,4-difluoro-phenylamino)-phenyl]-methanone

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 887MethanolSolvent

Procedure

Compound 493 (6.0 g, 14.9 mmol) was dissolved in MeOH (350 mL). Zinc-dust (12.69 g, 194 mmol) and NH4Cl (5.59 g, 104 mmol) were added. The reaction mixture was heated at reflux temperature for 1 h. The mixture was filtered and washed with MeOH. The filtrate was concentrated and the solid was dissolved in EtOAc (150 mL) and saturated aqueous Na2CO3 (100 mL). The water phase was extracted with EtOAc and the combined organic phases were dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by flash chromatography using EtOAc/petroleum ether (40-60) 1:2 as the eluent to afford the title compound as a slightly coloured crystalline compound.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux temperature for 1 h
  3. filtrationThe mixture was filtered
  4. washwashed with MeOH
  5. concentrationThe filtrate was concentrated
  6. dissolutionthe solid was dissolved in EtOAc (150 mL)
  7. extractionThe water phase was extracted with EtOAc
  8. dry with materialthe combined organic phases were dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-960b8320cb0d4079b11a85a06b82281a
Source dataset
uspto-grants-2011_07
Patent number
US07977387B2

Linked notes

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