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

HRID 20726Notes

Reaction equation

HRID 20726 reaction equation
[F:1][C:2]1[C:3]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([I:29])=[CH:25][C:24]=2[F:30])=[C:4]([CH:12]=[C:13](/[CH:16]=[N:17]/[O:18][CH2:19][CH2:20][OH:21])[C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6].FC(F)(F)C(O)=O.C([BH3-])#N.[Na+].O>CO>[F:1][C:2]1[C:3]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([I:29])=[CH:25][C:24]=2[F:30])=[C:4]([CH:12]=[C:13]([CH2:16][NH:17][O:18][CH2:19][CH2:20][OH:21])[C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6]

Participants

6

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 5003444Sodium cyanoborohydrideHCID 113072243,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-5-[(E)-2-hydroxyethoxyiminomethyl]benzamide

Product 1

HCID 115774573,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(2-hydroxy-ethoxyamino)-methyl]-benzamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (E)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(2-hydroxy-ethoxyimino)-methyl]-benzamide (3.62 g, 6.70 mmol) obtained in Step B in methanol (100 ml) were added portionwise trifluoroacetic acid (6.5 ml) and sodium cyanoborohydride (3.78 g, 60.2 mmol) over 2 days while monitoring the progression of the reaction by TLC. The reaction mixture was poured into water, and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (CH2Cl2/MeOH (15:1)), and the resultant crude compound was crystallized from methylene chloride to give 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(2-hydroxy-ethoxyamino)-methyl]-benzamide (1.66 g, 46%, as a total of first and second crystals).

Workup

  1. customthe progression of the reaction by TLC
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated aqueous sodium bicarbonate
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (CH2Cl2/MeOH (15:1))
  7. customthe resultant crude compound was crystallized from methylene chloride

Sources & evidence

ORD record
ord-7d9fb428ff414262adbf4997cde31aae
Source dataset
uspto-grants-2010_06
Patent number
US07745663B2

Reaction notes

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