Tetrabutylammonium Fluoride → 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-[(2-hydroxy-acetylamino)-methyl]-N-(2-hydroxy-ethoxy)-benzamide

HRID 20777Notes

Reaction equation

HRID 20777 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C([Si](C)(C)[O:24][CH2:25][CH2:26][O:27][NH:28][C:29](=[O:53])[C:30]1[CH:35]=[C:34]([CH2:36][NH:37][C:38](=[O:41])[CH2:39][OH:40])[C:33]([F:42])=[C:32]([F:43])[C:31]=1[NH:44][C:45]1[CH:50]=[CH:49][C:48]([I:51])=[CH:47][C:46]=1[F:52])(C)(C)C>O1CCCC1>[F:43][C:32]1[C:31]([NH:44][C:45]2[CH:50]=[CH:49][C:48]([I:51])=[CH:47][C:46]=2[F:52])=[C:30]([CH:35]=[C:34]([CH2:36][NH:37][C:38](=[O:41])[CH2:39][OH:40])[C:33]=1[F:42])[C:29]([NH:28][O:27][CH2:26][CH2:25][OH:24])=[O:53]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 59348018HCID 59348018, compound

Product 1

HCID 115194943,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-[(2-hydroxy-acetylamino)-methyl]-N-(2-hydroxy-ethoxy)-benzamideYield 39%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Tetra-n-butylammonium fluoride (1 mol/L solution in tetrahydrofuran, 0.5 mL, 0.500 mmol) was added to a solution of N-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-[(2-hydroxy-acetylamino)-methyl]-benzamide (4.34 mg, 0.00665 mmol) obtained in Step C in tetrahydrofuran (anhydrous, 1 mL) at room temperature. The mixture was stirred for 1.5 hours. After completion of the reaction, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, and evaporated under reduced pressure. The resultant crude product was purified sequentially with silica gel flash chromatography (Mega Bond Elut, Varian, 5% methanol/methylene chloride as an eluent) and preparative TLC (No. 5715, Merck, 7% methanol/methylene chloride as a developing solvent) to give 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-[(2-hydroxy-acetylamino)-methyl]-N-(2-hydroxy-ethoxy)-benzamide (Compound E-5, 1.4 mg, 39%) 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 water and saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customevaporated under reduced pressure
  6. customThe resultant crude product was purified sequentially with silica gel flash chromatography (Mega Bond Elut, Varian, 5% methanol/methylene chloride as an eluent) and preparative TLC (No

Sources & evidence

ORD record
ord-03344a507615451a9b0ec54744d3f00e
Source dataset
uspto-grants-2010_06
Patent number
US07745663B2

Reaction notes

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