Hydrochloric Acid → [2-Chloro-4-(2,4-difluoro-phenylamino)-phenyl]-(5-iodo-2-methyl-phenyl)-methanone

HRID 1012611Notes

Reaction equation

HRID 1012611 reaction equation
N[C:2]1[CH:3]=[CH:4][C:5]([CH3:26])=[C:6]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=3[F:24])=[CH:12][C:11]=2[Cl:25])=[O:9])[CH:7]=1.Cl.N([O-])=O.[Na+].[I:32]I>CC(C)=O.O.CCOC(C)=O>[Cl:25][C:11]1[CH:12]=[C:13]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=2[F:24])[CH:14]=[CH:15][C:10]=1[C:8]([C:6]1[CH:7]=[C:2]([I:32])[CH:3]=[CH:4][C:5]=1[CH3:26])=[O:9]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 807IodineHCID 11538012(5-Amino-2-methyl-phenyl)-[2-chloro-4-(2,4-difluoro-phenylamino)-phenyl]-methanoneHCID 23668193Sodium Nitrite

Product 1

HCID 67314444[2-Chloro-4-(2,4-difluoro-phenylamino)-phenyl]-(5-iodo-2-methyl-phenyl)-methanone

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

Compound 494 (0.62 g, 1.66 mmol) was dissolved in acetone (14 mL). Concentrated HCl (37%, 0.69 mL, 8.3 mmol) was added and the solution was cooled on an ice bath. NaNO2 (0.14 g, 1.99 mmol) was dissolved in H2O (1 mL) and added to the above solution during 15 minutes. The internal temperature was kept at 0° C.-2° C. during the addition. The suspension was stirred on an ice bath for 0.5 h, after which a solution of KI (0.41 g, 2.45 mmol) and I2 (0.31 g, 1.22 mmol) in H2O (4 mL) was added drop wise during 5 minutes. The mixture was stirred at 0° C. for 2 h. H2O (20 mL) and EtOAc (20 mL) was added and stirred and the phases were separated. The organic phase was washed with aqueous NaHSO3, then with aqueous Na2CO3, dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by flash chromatography using EtOAc/petroleum ether (40-60) 1:5 to afford the title compound as a slightly coloured crystalline compound.

Workup

  1. temperaturethe solution was cooled on an ice bath
  2. additionadded to the above solution during 15 minutes
  3. additionThe internal temperature was kept at 0° C.-2° C. during the addition
  4. stirringThe mixture was stirred at 0° C. for 2 h
  5. stirringstirred
  6. customthe phases were separated
  7. washThe organic phase was washed with aqueous NaHSO3
  8. dry with materialwith aqueous Na2CO3, dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-bea33bd622c74073898e90ead125a71b
Source dataset
uspto-grants-2011_07
Patent number
US07977387B2

Reaction notes

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