Chloride → (R)-1-(3-(9H-tribenz[b,d,f]azepin-9-yl)propyl)-3-piperidine carboxylic acid ethyl ester hydrochloride

HRID 1290660Notes

Reaction equation

HRID 1290660 reaction equation
[Cl-:1].[C:2]([CH:5]([CH:7]([C:9](O)=O)O)O)(O)=O.[NH:12]1[CH2:17][CH2:16][CH2:15][C@@H:14]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:13]1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[CH3:31][C:32](=O)[CH2:33][CH3:34]>ClCCl>[ClH:1].[CH2:21]([O:20][C:18]([C@@H:14]1[CH2:15][CH2:16][CH2:17][N:12]([CH2:18][CH2:14][CH2:13][N:12]2[C:33]3[CH:34]=[CH:2][CH:5]=[CH:7][C:32]=3[C:31]3[CH:15]=[CH:16][CH:17]=[CH:9][C:7]=3[C:5]3[CH:31]=[CH:32][CH:33]=[CH:34][C:2]2=3)[CH2:13]1)=[O:19])[CH3:22]

Participants

7

Reactant 5

HCID 312ChlorideHCID 4875Potassium IodideHCID 6569Methyl Ethyl KetoneHCID 11430Potassium CarbonateHCID 2733695(R)-(-)-Ethyl Nipecotate Tartrate

Product 1

HCID 70197521(R)-1-(3-(9H-tribenz[b,d,f]azepin-9-yl)propyl)-3-piperidine carboxylic acid ethyl ester hydrochlorideYield 41%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of the above chloride (0.21 g, 0.66 mmol), ethyl (R)-3-piperidinecarboxylate tartrate (0.30 g, 1.0 mmol), potassium carbonate (0.18 g, 2.0 mmol), potassium iodide (0.10 g, 0.60 mmol) and 2-butanone (10 ml) was heated at reflux temperature for 40 hours. After cooling to room temperature, dichloromethane (50 ml) was added and the mixture was filtered. The filtrate was washed with 1N hydrochloric acid (20 ml), water (20 ml) and saturated sodium hydrogencarbonate solution (20 ml), dried over sodium sulfate and evaporated in vacuo. The remainder was dissolved in diethyl ether (20 ml) and a 2.6M solution of hydrogen chloride in diethyl ether (0.5 ml) was added. The formed precipitate was collected by filtration, washed with ether and dried, affording 0.13 g (41%) of (R)-1-(3-(9H-tribenz[b,d,f]azepin-9-yl)propyl)-3-piperidine carboxylic acid ethyl ester hydrochloride as a solid.

Workup

  1. temperaturewas heated
  2. temperatureat reflux temperature for 40 hours
  3. filtrationthe mixture was filtered
  4. washThe filtrate was washed with 1N hydrochloric acid (20 ml), water (20 ml) and saturated sodium hydrogencarbonate solution (20 ml)
  5. dry with materialdried over sodium sulfate
  6. customevaporated in vacuo
  7. dissolutionThe remainder was dissolved in diethyl ether (20 ml)
  8. additiona 2.6M solution of hydrogen chloride in diethyl ether (0.5 ml) was added
  9. filtrationThe formed precipitate was collected by filtration
  10. washwashed with ether
  11. customdried

Sources & evidence

ORD record
ord-32652ec9efcc475c9fd1bb390b07416c
Source dataset
uspto-grants-1998_05
Patent number
US05753643

Reaction notes

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