Potassium Phosphate, Tribasic → 6-(2-Fluorophenethyl)-9-chloro-1,2,3,4,5,6-hexahydro-3-methylazepino[4,5-b]indole

HRID 1481411Notes

Reaction equation

HRID 1481411 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][N:13]([CH3:16])[CH2:14][CH2:15][C:5]=3[C:4]=2[CH:3]=1.N1CCC[C@H]1C(O)=O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].Br[CH2:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[F:42]>CN(C=O)C.[Cu](I)I.O>[F:42][C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=1[CH2:35][CH2:34][N:7]1[C:8]2[CH:9]=[CH:10][C:2]([Cl:1])=[CH:3][C:4]=2[C:5]2[CH2:15][CH2:14][N:13]([CH3:16])[CH2:12][CH2:11][C:6]1=2

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 27569642-Fluorophenethyl bromideHCID 685585079-Chloro-3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole

Product 1

HCID 593683056-(2-Fluorophenethyl)-9-chloro-1,2,3,4,5,6-hexahydro-3-methylazepino[4,5-b]indole

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

The title compound was prepared by following general procedure 4. 9-Chloro-3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (234 mg, 1.0 mmol) was taken with copper iodide (19 mg, 0.1 mmol), L-proline (23 mg, 0.2 mmol), potassium phosphate tribasic (426 mg, 2.0 mmol) and then 1-(2-bromoethyl)-2-fluorobenzene (203 mg, 1 mmol) in DMF. The reaction mixture was stirred at 90° C. under argon atmosphere for 12 h and monitored by LCMS. After completion of the reaction, water was added and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over sodium sulfate and concentrated under vacuum. The crude product was purified by column chromatography (silica gel 100-200 mesh) (gradient 5% MeOH:DCM). The pure product was converted to its oxalate salt using oxalic acid and THF.

Workup

  1. additionwas added
  2. extractionextracted with ethyl acetate
  3. washThe ethyl acetate layer was washed with water
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe crude product was purified by column chromatography (silica gel 100-200 mesh) (gradient 5% MeOH:DCM)

Sources & evidence

ORD record
ord-56ea9ff73423472fba31f721cfe7f490
Source dataset
uspto-grants-2016_08
Patent number
US09409910B2

Reaction notes

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