Potassium Iodide → 1-(3-(10,11-dihydro-5H-dibenz[b,f]-azepin-5-yl)-1-propyl)-3-piperidine-acetic acid ethyl ester

HRID 363311

Reaction equation

HRID 363311 reaction equation
[I-].[K+].Cl[CH2:4][CH2:5][CH2:6][N:7]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[CH2:11][CH2:10][C:9]2[CH:18]=[CH:19][CH:20]=[CH:21][C:8]1=2.C(=O)([O-])[O-].[K+].[K+].Cl.[CH2:29]([O:31][C:32](=[O:40])[CH2:33][CH:34]1[CH2:39][CH2:38][CH2:37][NH:36][CH2:35]1)[CH3:30]>C(C(C)=O)C>[CH2:29]([O:31][C:32](=[O:40])[CH2:33][CH:34]1[CH2:39][CH2:38][CH2:37][N:36]([CH2:4][CH2:5][CH2:6][N:7]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[CH2:11][CH2:10][C:9]3[CH:18]=[CH:19][CH:20]=[CH:21][C:8]2=3)[CH2:35]1)[CH3:30]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 2867795-(3-Chloropropyl)-10,11-dihydro-5H-dibenz[b,f]azepineHCID 44118456Ethyl 2-(piperidin-3-yl)acetate hydrochloride

Product 1

HCID 536811681-(3-(10,11-dihydro-5H-dibenz[b,f]-azepin-5-yl)-1-propyl)-3-piperidine-acetic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent2×

Procedure

A mixture of potassium iodide (19.2 g, 0.12 mol) and methyl ethyl ketone (180 ml) was heated at reflux temperature for 1 h. A solution of 5-(3-chloropropyl)-10,11-dihydro-5H-dibenz[b,f]azepine (5.2 g, 0.019 mol, prepared similarly as described in example 1) in methyl ethyl ketone (25 ml) was added and heating at reflux temperature was continued for 3 h. Potassium carbonate (9.3 g, 0.067 mol) and 3-piperidineacetic acid ethyl ester hydrochloride (5.6 g, 0.027 mol) were added and the reaction mixture was heated at reflux temperature for 2 h. The temperature was lowered to just below reflux and the mixture was left with stirring overnight. After cooling, the reaction mixture was filtered (Hyflo) and the solvent was evaporated in vacuo. The residue was purified by flash chromatography on silica gel (225 g) using a mixture of heptane and ethyl acetate (1:1) as eluent, to give 5.0 g of 1 -(3-(10,11-dihydro-5H-dibenz[b,f]-azepin-5-yl)-1-propyl)-3-piperidine-acetic acid ethyl ester as an oil.

Workup

  1. temperaturewas heated
  2. temperatureat reflux temperature for 1 h
  3. additionwas added
  4. temperatureheating
  5. temperatureat reflux temperature
  6. temperaturethe reaction mixture was heated
  7. temperatureat reflux temperature for 2 h
  8. temperaturebelow reflux
  9. waitthe mixture was left
  10. temperatureAfter cooling
  11. filtrationthe reaction mixture was filtered (Hyflo)
  12. customthe solvent was evaporated in vacuo
  13. customThe residue was purified by flash chromatography on silica gel (225 g)
  14. additiona mixture of heptane and ethyl acetate (1:1) as eluent

Sources & evidence

ORD record
ord-8a74f23f3cae4764890808ea48b3e533
Source dataset
uspto-grants-1999_02
Patent number
US05874428

Linked notes

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