4-Methylmorpholine → HCID 22271590, compound

HRID 2218485Notes

Reaction equation

HRID 2218485 reaction equation
FC1C(O[C:9](=[O:27])[C:10]2[CH:15]=[CH:14][C:13]([F:16])=[C:12]([F:17])[C:11]=2[NH:18][C:19]2[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=2[F:26])=C(F)C(F)=C(F)C=1F.[Cl-].[OH:33][CH:34]1[CH2:38][O:37][NH2+:36][CH2:35]1.CN1CCOCC1.C(OCC)(=O)C>CN(C)C=O>[F:17][C:12]1[C:11]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=2[F:26])=[C:10]([C:9]([N:36]2[CH2:35][CH:34]([OH:33])[CH2:38][O:37]2)=[O:27])[CH:15]=[CH:14][C:13]=1[F:16]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 8857Ethyl AcetateHCID 276390382409-18-5HCID 23398483HCID 23398483, compound

Product 1

HCID 22271590HCID 22271590, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirring solution of 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzoic acid pentafluorophenyl ester (171 mg, 0.306 mmol) and 4-hydroxytetrahydroisoxazol-2-ium chloride (BIONET, 58 mg, 0.46 mmol) in dimethylformamide (2 mL) was added 4-methylmorpholine (0.1 mL, 0.91 mmol). The resultant reaction mixture was stirred at ambient temperature for 3 h. Ethyl acetate (50 mL) was added the mixture was washed with water (3×10 mL) and saturated brine solution (10 mL). The extracts were dried over magnesium sulfate and concentrated in vacuo. Chromatography (10% methanol-dichloromethane) afforded a tan-colored oil that solidified upon standing. Recrystallization from acetone-ether afforded [3,4-Difluoro-2-(2-fluoro-4-iodo-phenylamino)-phenyl]-(4-hydroxy-isoxazolidin-2-yl)-methanone (61 mg, 43% yield) as a white powder:

Workup

  1. customThe resultant reaction mixture
  2. washwas washed with water (3×10 mL) and saturated brine solution (10 mL)
  3. dry with materialThe extracts were dried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customChromatography (10% methanol-dichloromethane) afforded a tan-colored oil that
  6. customRecrystallization from acetone-ether

Sources & evidence

ORD record
ord-824c7de6b06b4911bff105aa6cb94b0f
Source dataset
uspto-grants-2008_08
Patent number
US07411001B2

Reaction notes

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