Cesium carbonate → 1-({3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(trifluoromethyl)azetidin-3-ol

HRID 1808950Notes

Reaction equation

HRID 1808950 reaction equation
[F:1][C:2]1[C:3]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=2[F:24])=[C:4]([C:9]([N:11]2[CH2:14][C:13](=[O:15])[CH2:12]2)=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[F:25][C:26]([Si](C)(C)C)([F:28])[F:27].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[F:1][C:2]1[C:3]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=2[F:24])=[C:4]([C:9]([N:11]2[CH2:12][C:13]([C:26]([F:28])([F:27])[F:25])([OH:15])[CH2:14]2)=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 552549(Trifluoromethyl)trimethylsilaneHCID 16223411{3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonylazetidin-3-one

Product 1

HCID 162234141-({3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(trifluoromethyl)azetidin-3-olYield 69%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-one (25 mg, 0.056 mmol), prepared using procedures described in Example 6, was taken into DMF (0.5 mL) followed by addition of (trifluoromethyl)trimethylsilane (40 μL, 0.28 mmol) and cesium carbonate (22 mg, 0.067 mmol) and the mixture was stirred for one hour at room temperature. The mixture was partitioned with ethyl ether and water and the organic phase washed three times with additional water then brine and dried over anhydrous sodium sulfate. Filtration and concentration followed by silica gel flash chromatography of the residue using hexanes:ethyl acetate 3:2 as eluent afforded 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(trifluoromethyl)azetidin-3-ol (19.8 mg, 69% yield) as a colorless crystalline solid. 1H-NMR (400 MHz, CDCl3): 8.31-8.26 (br, 1H), 7.40 (d, 1H), 7.33 (d, 1H), 7.13-7.10 (m, 1H), 6.86-6.80 (m, 1H), 6.65-6.60 (m, 1H), 4.42 (br s, 2H), 4.18 (br s, 2H). MS (EI) for C17H11F6IN2O2: 517 (MH+).

Workup

  1. customThe mixture was partitioned with ethyl ether and water
  2. washthe organic phase washed three times with additional water
  3. dry with materialbrine and dried over anhydrous sodium sulfate
  4. filtrationFiltration and concentration

Sources & evidence

ORD record
ord-471bcd3c2cc2454bb00a81f9ccdbc632
Source dataset
uspto-grants-2013_01
Patent number
US08362002B2

Reaction notes

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