Tributylvinyltin → HCID 69417337, compound

HRID 1373200Notes

Reaction equation

HRID 1373200 reaction equation
[CH3:1][O:2][C:3]([C:5]1([F:24])[C:14]([NH:15][C:16]2[CH:21]=[CH:20][C:19](I)=[CH:18][C:17]=2[F:23])=[CH:13][C:8]2=[N:9][CH2:10][N:11]([CH3:12])[C:7]2=[CH:6]1)=[O:4].[CH:25]([Sn](CCCC)(CCCC)CCCC)=[CH2:26]>O1CCOCC1>[CH3:1][O:2][C:3]([C:5]1([F:24])[C:14]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([CH:25]=[CH2:26])=[CH:18][C:17]=2[F:23])=[CH:13][C:8]2=[N:9][CH2:10][N:11]([CH3:12])[C:7]2=[CH:6]1)=[O:4]

Participants

4

Reactant 2

HCID 81998TributylvinyltinHCID 68804660HCID 68804660, compound

Product 1

HCID 69417337HCID 69417337, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 5-Fluoro-6-(2-fluoro-4-iodo-phenylamino)-3-methyl-3H-benzoimidazole-5-carboxylic acid methyl ester (6.36 g, 14.4 mmol) and vinyl tributylstannane (5.0 g, 15.8 mmol) in dioxane (100 mL) was de-gassed by freeze-pump-thaw cycle (twice). Tetrakis(triphenylphoshine)palladium was added and the reaction mixture was refluxed under an atmosphere of nitrogen until mass spectrometry indicated complete consumption of the aryl iodide. The reaction mixture was allowed to cool to ambient temperature and was filtered through a pad of Celite and washed with ethyl acetate (255 mL). Aqueous potassium fluoride (1M, 50 mL) was added to the filtrate and the biphasic mixture was shaken. The resultant precipitate was removed by filtration and the organics were further washed with aqueous potassium fluoride (1M, 50 mL), water (2×100 mL), and saturated brine (100 mL). The solution was dried over anhydrous sodium sulfate, concentrated in vacuo and chromatographed on silica gel. Elution with ethyl acetate afforded 5-Fluoro-6-(2-fluoro-4-vinyl-phenylamino)-3-methyl-3H-benzoimidazole-5-carboxylic acid methyl ester (2.13 g, 44% yield): 1H NMR (400 MHz, DMSO-d6) δ 8.44 (s, 1 H), 8.09 (br s, 1 H), 8.06 (s, 1 H), 5.36 (dd, J=13.2, 1.5 Hz, 1 H), 5.05 (dd, J=8.3, 1.5 Hz, 1 H), 6.60 (dd, J=15.5, 10.9 Hz, 1 H), 6.50 (td, J=8.8, 4.6 Hz, 1 H), 5.65 (d, J=15.4 Hz, 1 H), 5.11 (d, J=11.2 Hz, 1 H), 3.92 (s, 3 H), 3.82 (s, 3 H).

Workup

  1. temperaturethe reaction mixture was refluxed under an atmosphere of nitrogen until mass spectrometry
  2. customconsumption of the aryl iodide
  3. filtrationwas filtered through a pad of Celite
  4. washwashed with ethyl acetate (255 mL)
  5. additionAqueous potassium fluoride (1M, 50 mL) was added to the filtrate
  6. customThe resultant precipitate was removed by filtration
  7. washthe organics were further washed with aqueous potassium fluoride (1M, 50 mL), water (2×100 mL), and saturated brine (100 mL)
  8. dry with materialThe solution was dried over anhydrous sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customchromatographed on silica gel
  11. washElution with ethyl acetate

Sources & evidence

ORD record
ord-b08828a073054c5b9bcef3182d50744f
Source dataset
uspto-grants-2007_01
Patent number
US07160915B2

Reaction notes

Loading…