Triethylsilane → 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(2-methanesulfonyl-ethoxymethyl)-benzamide

HRID 20757Notes

Reaction equation

HRID 20757 reaction equation
[F:1][C:2]1[C:3]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=2[F:26])=[C:4]([CH:12]=[C:13]([CH:16]=[O:17])[C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6].[CH3:27][S:28]([CH:31](O)[CH3:32])(=[O:30])=[O:29].C([SiH](CC)CC)C>C(Cl)Cl.FC(F)(F)S([O-])(=O)=O.[Cu+2].FC(F)(F)S([O-])(=O)=O>[F:1][C:2]1[C:3]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=2[F:26])=[C:4]([CH:12]=[C:13]([CH2:16][O:17][CH2:32][CH2:31][S:28]([CH3:27])(=[O:30])=[O:29])[C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6]

Participants

6

Reactant 3

HCID 12052TriethylsilaneHCID 21979976MethanesulfonylethanolHCID 231323883,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-formyl-N-(2-hydroxy-ethoxy)-benzamide

Product 1

HCID 116643063,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(2-methanesulfonyl-ethoxymethyl)-benzamideYield 21%

Reagents, catalysts & solvents 2

HCID 2734996copper(II) trifluoromethanesulfonateCatalystHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-formyl-N-(2-hydroxy-ethoxy)-benzamide (52 mg, 0.108 mmol) obtained in Step F of Example 1 in methylene chloride (anhydrous, 5 mL) were added copper trifluoromethanesulfonate (20 mg, 0.005 mmol), methanesulfonylethanol (200 μL), and triethylsilane (500 μL, 3.13 mmol) under a nitrogen atmosphere, and the mixture was stirred thoroughly for a whole day and night. After completion of the reaction, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed sequentially with 2% aqueous EDTA, water, and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resultant residue was purified by preparative TLC (No. 5744, Merck, 5% methanol/methylene chloride as a developing solvent) to give 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(2-methanesulfonyl-ethoxymethyl)-benzamide (13.3 mg, 21%) as a white solid.

Workup

  1. customAfter completion of the reaction
  2. extractionthe reaction mixture was extracted with ethyl acetate
  3. washthe organic layer was washed sequentially with 2% aqueous EDTA, water, and saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resultant residue was purified by preparative TLC (No

Sources & evidence

ORD record
ord-884dd8e48151401d84fc02262362e6a1
Source dataset
uspto-grants-2010_06
Patent number
US07745663B2

Reaction notes

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