Dimethylformamide → N,N-dimethyl-5-ethyl-2-(4'-chloro-2'-fluoro-6'-methylanilino)phenylacetamide

HRID 382496Notes

Reaction equation

HRID 382496 reaction equation
[CH3:1][N:2]([CH3:24])[C:3](=[O:23])[CH2:4][C:5]1[CH:10]=[C:9]([CH2:11][CH3:12])[CH:8]=[CH:7][C:6]=1[NH:13][C:14]1[C:19]([F:20])=[CH:18][C:17]([Cl:21])=[CH:16][C:15]=1Br.[CH3:25]N(C=O)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C[Sn](C)(C)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O.C(N(CC)CC)C>[CH3:1][N:2]([CH3:24])[C:3](=[O:23])[CH2:4][C:5]1[CH:10]=[C:9]([CH2:11][CH3:12])[CH:8]=[CH:7][C:6]=1[NH:13][C:14]1[C:15]([CH3:25])=[CH:16][C:17]([Cl:21])=[CH:18][C:19]=1[F:20]

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 11661TetramethyltinHCID 80271Tri-o-tolylphosphineHCID 86584270N,N-dimethyl-5-ethyl-2-(2'-bromo-4'-chloro-6'-fluoroanilino)phenylacetamide

Product 1

HCID 21938655N,N-dimethyl-5-ethyl-2-(4'-chloro-2'-fluoro-6'-methylanilino)phenylacetamide

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

N,N-Dimethyl-5-ethyl-2-(2′-bromo-4′-chloro-6′-fluoroanilino)phenylacetamide (2.5 g, 6.0 mmol) is combined with DMF (10 ml), triethylamine (10 ml), tri-o-tolylphosphine (0.5 g, 1.6 mmol), tetramethyltin (4 ml, 5.16 g, 28.9 mmol) and palladium acetate (0.25 g, 1.1 mmol), and the mixture heated in a sealed tube for 3 days at 95°. The tube is allowed to cool and carefully opened. Water and ethyl acetate are added to the reaction and the mixture separated. The organic fraction is washed with a dilute NaCl solution (2×50 ml). The combined aqueous fractions are then washed with ethyl acetate and the combined organic fractions are then dried (magnesium sulfate). The material is absorbed onto a small amount of silica gel and purified by flash chromatography (on silica, ethyl acetate:hexanes, 1:4 to 1:1) to give N,N-dimethyl-5-ethyl-2-(4′-chloro-2′-fluoro-6′-methylanilino)phenylacetamide.

Workup

  1. temperaturethe mixture heated in a sealed tube for 3 days at 95°
  2. temperatureto cool
  3. customthe mixture separated
  4. washThe organic fraction is washed with a dilute NaCl solution (2×50 ml)
  5. washThe combined aqueous fractions are then washed with ethyl acetate
  6. dry with materialthe combined organic fractions are then dried (magnesium sulfate)
  7. customThe material is absorbed onto a small amount of silica gel
  8. custompurified by flash chromatography (on silica, ethyl acetate:hexanes, 1:4 to 1:1)

Sources & evidence

ORD record
ord-8a9365f617a941cab058907f812a2932
Source dataset
uspto-grants-2001_10
Patent number
US06310099B1

Reaction notes

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