Dimethylformamide → 3-[4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl]-6-fluoro-1-(2,2,2-trifluoroethyl)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one

HRID 2035696Notes

Reaction equation

HRID 2035696 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[CH:9])=[CH:4][CH:3]=1.O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+].[N:23]([CH:26]1[CH2:32][CH2:31][C:30]2[C:33]([F:37])=[CH:34][CH:35]=[CH:36][C:29]=2[N:28]([CH2:38][C:39]([F:42])([F:41])[F:40])[C:27]1=[O:43])=[N+:24]=[N-:25].CN(C=O)C>O.CCOC(C)=O.CCO>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:25]=[N:24][N:23]([CH:26]3[CH2:32][CH2:31][C:30]4[C:33]([F:37])=[CH:34][CH:35]=[CH:36][C:29]=4[N:28]([CH2:38][C:39]([F:40])([F:41])[F:42])[C:27]3=[O:43])[CH:9]=2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 136603Benzene, 1-bromo-4-ethynyl-HCID 23667548Sodium AscorbateHCID 580635233-azido-6-fluoro-1-(2,2,2-trifluoroethyl)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one

Product 1

HCID 580635063-[4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl]-6-fluoro-1-(2,2,2-trifluoroethyl)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-oneYield 75.2%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

1-Bromo-4-ethynylbenzene (271 mg, 1.499 mmol), cupric sulfate (65.2 mg, 0.409 mmol), sodium ascorbate (108 mg, 0.545 mmol), and 3-azido-6-fluoro-1-(2,2,2-trifluoroethyl)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one (300 mg, 1.362 mmol) in 6.6 mL of a 1:1:1 solution of DMF:EtOH:H2O was stirred for 25 mins. The mixture was diluted with water before EtOAc was added to extract the product. The organic phase was separated and washed with water (2×) and brine (1×) before being dried with Na2SO4 and evaporated to afford an oil. This material was chromatographed on silica (0-80% EtOAc in hexanes) to yield 3-[4-(4-bromophenyl)-1H-1,2,3-triazol-1-yl]-6-fluoro-1-(2,2,2-trifluoroethyl)-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one (495.1 mg) as a solid.

Workup

  1. additionwas added
  2. extractionto extract the product
  3. customThe organic phase was separated
  4. washwashed with water (2×) and brine (1×)
  5. dry with materialbefore being dried with Na2SO4
  6. customevaporated
  7. customto afford an oil
  8. customThis material was chromatographed on silica (0-80% EtOAc in hexanes)

Sources & evidence

ORD record
ord-baa6c272df804e86a0f909c0b52c8409
Source dataset
uspto-grants-2013_11
Patent number
US08575150B2

Reaction notes

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