Potassium Phosphate, Tribasic → (E)-6-(2-(3,4-difluorophenyl)prop-1-enyl)-1,2,3,4,5,6-hexahydro-3,9-dimethylazepino[4,5-b]indole

HRID 1481465Notes

Reaction equation

HRID 1481465 reaction equation
[CH3:1][N:2]1[CH2:15][CH2:14][C:13]2[C:12]3[CH:11]=[C:10]([CH3:16])[CH:9]=[CH:8][C:7]=3[NH:6][C:5]=2[CH2:4][CH2:3]1.N1CCC[C@H]1C(O)=O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].Br[CH:34]=[C:35]([C:37]1[CH:42]=[CH:41][C:40]([F:43])=[C:39]([F:44])[CH:38]=1)[CH3:36]>CN(C=O)C.[Cu]I>[F:44][C:39]1[CH:38]=[C:37](/[C:35](/[CH3:36])=[CH:34]/[N:6]2[C:7]3[CH:8]=[CH:9][C:10]([CH3:16])=[CH:11][C:12]=3[C:13]3[CH2:14][CH2:15][N:2]([CH3:1])[CH2:3][CH2:4][C:5]2=3)[CH:42]=[CH:41][C:40]=1[F:43]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 685600921,2,3,4,5,6-Hexahydro-3,9-dimethylazepino[4,5-b]indoleHCID 866355044-(1-Bromoprop-1-en-2-yl)-1,2-difluorobenzene

Product 1

HCID 59368443(E)-6-(2-(3,4-difluorophenyl)prop-1-enyl)-1,2,3,4,5,6-hexahydro-3,9-dimethylazepino[4,5-b]indole

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Procedure

3,9-Dimethyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (77 mg, 0.36 mmol) was dissolved in DMF (6 mL). Copper (I) iodide (8 mg, 0.036 mmol), L-proline (9 mg, 0.086 mmol) and K3PO4 (183 mg, 0.86 mmol) were added and the reaction mixture was stirred for 10 min at RT. 4-(1-Bromoprop-1-en-2-yl)-1,2-difluorobenzene (100 mg, 0.43 mmol) was added dropwise and the reaction mixture was purged with nitrogen. The reaction mixture was heated at 80° C. for overnight (prolonged heating in some cases was required). The DMF was evaporated under reduced pressure, the residue was diluted with water and the solid was filtered. The solid material was purified by silica gel chromatography (100-200 mesh). Yield: 52 mg. 1HNMR (CD3OD, Oxalate salt) δ (ppm): 7.60 (m, 1H), 7.50 (m, 1H), 7.30 (m, 2H), 7.0 (s, 3H), 3.60 (m, 4H), 3.25 (m, 4H), 3.05 (s, 3H), 2.42 (s, 3H), 1.90 (s, 3H).

Workup

  1. customthe reaction mixture was purged with nitrogen
  2. temperatureThe reaction mixture was heated at 80° C. for overnight (
  3. temperatureprolonged heating in some cases
  4. customThe DMF was evaporated under reduced pressure
  5. additionthe residue was diluted with water
  6. filtrationthe solid was filtered
  7. customThe solid material was purified by silica gel chromatography (100-200 mesh)

Sources & evidence

ORD record
ord-ba89e7ec96c3421491feb79c2cbdb445
Source dataset
uspto-grants-2016_08
Patent number
US09409910B2

Reaction notes

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