Water → N-[2-(t-butyldimethylsilanyloxy)-ethoxy]-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-5-(hydroxyiminomethyl)-benzamide

HRID 661717Notes

Reaction equation

HRID 661717 reaction equation
[Si:1]([O:8][CH2:9][CH2:10][O:11][NH:12][C:13](=[O:33])[C:14]1[CH:19]=[C:18]([CH:20]=O)[C:17]([F:22])=[C:16]([F:23])[C:15]=1[NH:24][C:25]1[CH:30]=[CH:29][C:28]([I:31])=[CH:27][C:26]=1[F:32])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Cl.[NH2:35][OH:36].C(=O)(O)[O-].[Na+].O>C(O)C>[Si:1]([O:8][CH2:9][CH2:10][O:11][NH:12][C:13](=[O:33])[C:14]1[CH:19]=[C:18]([CH:20]=[N:35][OH:36])[C:17]([F:22])=[C:16]([F:23])[C:15]=1[NH:24][C:25]1[CH:30]=[CH:29][C:28]([I:31])=[CH:27][C:26]=1[F:32])([C:4]([CH3:6])([CH3:5])[CH3:7])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 23132329N-[2-(t-butyldimethylsilanyloxy)-ethoxy]-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-5-formyl-benzamide

Product 1

HCID 74020017N-[2-(t-butyldimethylsilanyloxy)-ethoxy]-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-5-(hydroxyiminomethyl)-benzamideYield 46.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

N-[2-(t-butyldimethylsilanyloxy)-ethoxy]-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-5-formyl-benzamide (10.5 mg, 17.7 μmol) prepared in Process B was dissolved in ethanol (1.5 ml). Hydroxylamine hydrochloride (40 mg, 0.57 mmol) and saturated aqueous solution of sodium bicarbonate (0.3 ml) were added thereto, and the mixture was stirred at room temperature for two hours. Water (5 ml) was added to the reaction solution, which was extracted with ethyl acetate (6 ml×3). The organic layers were combined, washed with saturated brine (8 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified with silica gel-column chromatography (Presep (r) silica gel, 10 g, Wako Pure Chemical Industries, Ltd., n-hexane/ethyl acetate (4:1)) to give N-[2-(t-butyldimethylsilanyloxy)-ethoxy]-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-5-(hydroxyiminomethyl)-benzamide (5.0 mg, 46%).

Workup

  1. extractionwas extracted with ethyl acetate (6 ml×3)
  2. washwashed with saturated brine (8 ml)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified with silica gel-column chromatography (Presep (r) silica gel, 10 g, Wako Pure Chemical Industries, Ltd., n-hexane/ethyl acetate (4:1))

Sources & evidence

ORD record
ord-6d42623e7e2c4627a27b0a1e67d2e94d
Source dataset
uspto-grants-2011_12
Patent number
US08084645B2

Reaction notes

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