Tetrahydrofuran → N-{3-fluoro-4-[(methylsulfonyl)amino]benzyl}-2-[4-(2,2,2-trifluoro-1,1-dimethylethy)phenoxy]acetamide

HRID 1350817Notes

Reaction equation

HRID 1350817 reaction equation
O1CCCC1.[F:6][C:7]([F:23])([F:22])[C:8]([C:11]1[CH:21]=[CH:20][C:14]([O:15][CH2:16][C:17]([OH:19])=O)=[CH:13][CH:12]=1)([CH3:10])[CH3:9].[Cl-].ClC1N(C)CC[NH+]1C.Cl.[NH2:34][CH2:35][C:36]1[CH:41]=[CH:40][C:39]([NH:42][S:43]([CH3:46])(=[O:45])=[O:44])=[C:38]([F:47])[CH:37]=1>C(N(CC)CC)C>[F:47][C:38]1[CH:37]=[C:36]([CH:41]=[CH:40][C:39]=1[NH:42][S:43]([CH3:46])(=[O:45])=[O:44])[CH2:35][NH:34][C:17](=[O:19])[CH2:16][O:15][C:14]1[CH:13]=[CH:12][C:11]([C:8]([CH3:9])([CH3:10])[C:7]([F:6])([F:23])[F:22])=[CH:21][CH:20]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 109867151H-Imidazolium, 2-chloro-4,5-dihydro-1,3-dimethyl-, chlorideHCID 21097486[4-(2,2,2-Trifluoro-1,1-dimethylethyl)phenoxy]acetic acidHCID 21097525N-[4-(aminomethyl)-2-fluorophenyl]methanesulfonamide hydrochloride

Product 1

HCID 21097515N-{3-fluoro-4-[(methylsulfonyl)amino]benzyl}-2-[4-(2,2,2-trifluoro-1,1-dimethylethy)phenoxy]acetamideYield 28.3%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

To a tetrahydrofuran (THF) (3.0 ml) solution of [4-(2,2,2-trifluoro-1,1-dimethylethyl)phenoxy]acetic acid (157 mg, 0.6 mmol) was added 2-chloro-1,3-dimethylimidazolinium chloride (CDI) (97 mg, 0.6 mmol) at room temperature and the mixture was stirred for 2 hours, followed by additional stirring for 10 hours with triethylamine (0.33 ml) and N-[4-(aminomethyl)-2-fluorophenyl]methanesulfonamide hydrochloride (122 mg, 0.48 mmol). The reaction was partitioned with water and methylene dichloride and the organic layer was separated, dried over sodium sulfate. After filtration to separate solvent and sodium sulfate, the solvent was removed under reduced pressure to give a residue, which was applied to a silica gel chromatography column and eluted with a volume mixture of methylene dichloride and methanol (5/1 to 5/2) to furnish 62.9 mg (28% yield) of the title compound as colorless oil.

Workup

  1. customThe reaction was partitioned with water and methylene dichloride
  2. customthe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. filtrationAfter filtration
  5. customto separate solvent and sodium sulfate
  6. customthe solvent was removed under reduced pressure
  7. customto give a residue, which
  8. washeluted with a volume mixture of methylene dichloride and methanol (5/1 to 5/2)

Sources & evidence

ORD record
ord-ea6cfc6e3474465fbc68d9fe6470bd68
Source dataset
uspto-grants-2007_05
Patent number
US07214824B2

Reaction notes

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