Acetic Acid → {4-[4-(5-chloro-1H-indol-3-yl)-piperidine-1-yl]-1-phenylcyclohexyl}-dimethylamine

HRID 2357432Notes

Reaction equation

HRID 2357432 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[C:11]1[CH2:12][CH2:13][NH:14][CH2:15][CH:16]=1.[CH3:17][N:18]([CH3:31])[C:19]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1.C(O)(=O)C>ClCCCl>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:11]1[CH2:12][CH2:13][N:14]([CH:22]2[CH2:21][CH2:20][C:19]([N:18]([CH3:31])[CH3:17])([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH2:24][CH2:23]2)[CH2:15][CH2:16]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 137487Cyclohexylamine, N,N-dimethyl-1-phenyl-HCID 30505325-chloro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole

Product 1

HCID 10458949{4-[4-(5-chloro-1H-indol-3-yl)-piperidine-1-yl]-1-phenylcyclohexyl}-dimethylamine

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

5-chloro-3-(1,2,3,6-tetrahydropyridine-4-yl)-1H-indole (218 mg, 1 mmole) and 4-dimethylamino-4-phenylcyclohexane (217 mg, 1 mmole) were dissolved in dry 1,2-dichloroethane (20 ml). Glacial acetic acid (1 mmole) and sodium triacetoxy boron hydride (300 mg, 1.4 mmole) were added to this mixture. The reaction mixture was then stirred for 24 hours at RT. The reaction mixture was worked up by distilling off the 1,2-dichloroethane and diluted with water (10 ml). The reaction mixture was adjusted to pH 11 with 5M NaOH and extracted with EE (3×20 ml). The organic phase was dried with Na2SO4 and concentrated by evaporation. The product was a mixture of two diastereoisomeric compounds, which were separated by chromatography with methanol. The non-polar diastereoisomer was obtained as a colourless oil in a yield of 210 mg (48%), and the polar diastereoisomer was obtained as a colourless oil in a yield of 80 mg (18%).

Workup

  1. distillationby distilling off the 1,2-dichloroethane
  2. additiondiluted with water (10 ml)
  3. extractionextracted with EE (3×20 ml)
  4. dry with materialThe organic phase was dried with Na2SO4
  5. concentrationconcentrated by evaporation
  6. additiona mixture of two diastereoisomeric compounds, which
  7. customwere separated by chromatography with methanol
  8. customThe non-polar diastereoisomer was obtained as a colourless oil in a yield of 210 mg (48%)
  9. customthe polar diastereoisomer was obtained as a colourless oil in a yield of 80 mg (18%)

Sources & evidence

ORD record
ord-9e61870cfa3b4e4e847dfbeca09ee405
Source dataset
uspto-grants-2010_07
Patent number
US07759385B2

Reaction notes

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