Cesium carbonate → 6-Fluoro-3-[4-(4-iodo-3-methoxy-phenyl)-1,2,3-triazol-1-yl]-1-(2,2,2-trifluoro-ethyl)-1,3,4,5-tetrahydro-1-benzazepin-2-one

HRID 2035701Notes

Reaction equation

HRID 2035701 reaction equation
[F:1][C:2]1[C:7]2[CH2:8][CH2:9][CH:10]([N:14]3[CH:18]=[C:17]([C:19]4[CH:24]=[CH:23][C:22]([I:25])=[C:21]([O:26][CH3:27])[CH:20]=4)[N:16]=[N:15]3)[C:11](=[O:13])[NH:12][C:6]=2[CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].FC(F)(F)S(O[CH2:40][C:41]([F:44])([F:43])[F:42])(=O)=O>C1COCC1.O>[F:1][C:2]1[C:7]2[CH2:8][CH2:9][CH:10]([N:14]3[CH:18]=[C:17]([C:19]4[CH:24]=[CH:23][C:22]([I:25])=[C:21]([O:26][CH3:27])[CH:20]=4)[N:16]=[N:15]3)[C:11](=[O:13])[N:12]([CH2:40][C:41]([F:44])([F:43])[F:42])[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 666838136-Fluoro-3-[4-(4-iodo-3-methoxy-phenyl)-1,2,3-triazol-1-yl]-1,3,4,5-tetrahydro-1-benzazepin-2-one

Product 1

HCID 666829706-Fluoro-3-[4-(4-iodo-3-methoxy-phenyl)-1,2,3-triazol-1-yl]-1-(2,2,2-trifluoro-ethyl)-1,3,4,5-tetrahydro-1-benzazepin-2-oneYield 90.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

6-Fluoro-3-[4-(4-iodo-3-methoxy-phenyl)-1,2,3-triazol-1-yl]-1,3,4,5-tetrahydro-1-benzazepin-2-one (20 g, 41.8 mmol) was suspended in THF and stirred at room temperature. Cesium carbonate (24.53 g, 75 mmol) was added, followed by 2,2,2-trifluoroethyl trifluoromethanesulfonate (14.56 g, 62.7 mmol). The mixture was heated to gentle reflux for 2 h. The reaction was diluted with water, and the aqueous layer was extracted with EtOAc. The combined organic fractions were dried over Na2SO4, filtered, and concentrated. The residue was purified on silica gel, gradient to 100% EtOAc/hexanes. 6-Fluoro-3-[4-(4-iodo-3-methoxy-phenyl)-1,2,3-triazol-1-yl]-1-(2,2,2-trifluoro-ethyl)-1,3,4,5-tetrahydro-1-benzazepin-2-one (21.3 g) was obtained as a colorless solid.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto gentle reflux for 2 h
  3. extractionthe aqueous layer was extracted with EtOAc
  4. dry with materialThe combined organic fractions were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified on silica gel, gradient to 100% EtOAc/hexanes

Sources & evidence

ORD record
ord-5c5a01ca600a4d9db4167f525db1518c
Source dataset
uspto-grants-2013_11
Patent number
US08575150B2

Reaction notes

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