Dichloroacetic Acid → 3,4-Difluoro-2-(2-fluoro-4-iodo-phenylamino)-n-(2-hydroxy-ethoxy)-5-[(2-methylsulfanyl-ethoxyamino)-methyl]-benzamide

HRID 20727

Reaction equation

HRID 20727 reaction equation
[F:1][C:2]1[C:3]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([I:30])=[CH:26][C:25]=2[F:31])=[C:4]([CH:12]=[C:13](/[CH:16]=[N:17]/[O:18][CH2:19][CH2:20][S:21][CH3:22])[C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6].ClC(Cl)C(O)=O>C(Cl)Cl>[F:1][C:2]1[C:3]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([I:30])=[CH:26][C:25]=2[F:31])=[C:4]([CH:12]=[C:13]([CH2:16][NH:17][O:18][CH2:19][CH2:20][S:21][CH3:22])[C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6]

Participants

4

Reactant 2

HCID 6597Dichloroacetic AcidHCID 114330433,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-5-[(E)-2-methylsulfanylethoxyiminomethyl]benzamide

Product 1

HCID 115849853,4-Difluoro-2-(2-fluoro-4-iodo-phenylamino)-n-(2-hydroxy-ethoxy)-5-[(2-methylsulfanyl-ethoxyamino)-methyl]-benzamideYield 104.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Namely, (E)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(2-methylsulfanyl-ethyoxyimino)-methyl]-benzamide (104.8 mg, 0.184 mmol) was dissolved in methylene chloride (anhydrous, 10 mL). Borane-pyridine complex (140 μL, 1.38 mmol) and then dichloroacetic acid (115 μL, 1.38 mmol) were added thereto with cooling the reaction vessel in an ice-bath under a nitrogen atmosphere. The ice-bath was removed, and the mixture was stirred at room temperature for 17 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 Na2SO4, and concentrated under reduced pressure. The resultant yellow residue was purified by silica gel column chromatography (Mega Bond Elut, Varian, 5% methanol/methylene chloride as an eluent). The resultant fraction was concentrated under reduced pressure and the oily residue was triturated with 5% ethyl acetate/hexane to give 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(2-methylsulfanyl-ethoxyamino)-methyl]-benzamide (110 mg) as a white solid.

Workup

  1. temperaturewith cooling the reaction vessel in an ice-bath under a nitrogen atmosphere
  2. customThe ice-bath was removed
  3. customAfter completion of the reaction
  4. extractionthe reaction mixture was extracted with ethyl acetate
  5. washthe organic layer was washed sequentially with water and saturated brine
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe resultant yellow residue was purified by silica gel column chromatography (Mega Bond Elut, Varian, 5% methanol/methylene chloride as an eluent)
  9. concentrationThe resultant fraction was concentrated under reduced pressure
  10. customthe oily residue was triturated with 5% ethyl acetate/hexane

Sources & evidence

ORD record
ord-1e69dbeb3ebd476eb9a8c6c12fb5304e
Source dataset
uspto-grants-2010_06
Patent number
US07745663B2

Linked notes

Loading…