Potassium Iodide → (R)-1-(3-(10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5-ylidene)-1-propyl)-2-piperidinecarboxylic acid ethyl ester

HRID 1420648Notes

Reaction equation

HRID 1420648 reaction equation
Br[CH2:2][CH2:3][CH:4]=[C:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH2:9][CH2:8][C:7]2[CH:16]=[CH:17][CH:18]=[CH:19][C:6]1=2.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Cl.[CH2:29]([O:31][C:32]([C@H:34]1[CH2:39][CH2:38][CH2:37][CH2:36][NH:35]1)=[O:33])[CH3:30]>C(C(C)=O)C.C(OCC)(=O)C>[CH2:29]([O:31][C:32]([C@H:34]1[CH2:39][CH2:38][CH2:37][CH2:36][N:35]1[CH2:2][CH2:3][CH:4]=[C:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH2:9][CH2:8][C:7]2[CH:16]=[CH:17][CH:18]=[CH:19][C:6]1=2)=[O:33])[CH3:30]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 17126855-(3-bromopropylidene)-10,11-dihydro-5H-dibenzo[a,d]cyclohepteneHCID 69945924Ethyl (2R)-piperidine-2-carboxylate--hydrogen chloride (1/1)

Product 1

HCID 53822264(R)-1-(3-(10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5-ylidene)-1-propyl)-2-piperidinecarboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 6569Methyl Ethyl KetoneSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-(3-Bromo-1-propylidene)-10,11-dihydro-5H-dibenzo[a,d]cycloheptene (2.7 g, 8.6 mmol, prepared as described in WO 9518793), potassium carbonate (7.14 g, 52 mmol), potassium iodide (1.4 g 8.6 mmol), and (R)-(+)-2-piperidine-carboxylic acid ethyl ester hydrochloride (3.3 g, 17 mmol) were mixed in methyl ethyl ketone (50 ml) and heated at reflux temperature for 3 days. After cooling to room temperature, ethyl acetate (100 ml) was added and the mixture was washed with water (2×100 ml). The organic phase was dried (MgSO4) and evaporated in vacuo. The residue was purified by column chromatography on silica gel (600 ml), using a mixture of ethyl acetate and heptane (1:4) as eluent. This afforded 2.62 9 (78%) of (R)-1-(3-(10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5-ylidene)-1-propyl)-2-piperidinecarboxylic acid ethyl ester as an oil.

Workup

  1. temperatureheated
  2. temperatureat reflux temperature for 3 days
  3. washthe mixture was washed with water (2×100 ml)
  4. dry with materialThe organic phase was dried (MgSO4)
  5. customevaporated in vacuo
  6. customThe residue was purified by column chromatography on silica gel (600 ml)
  7. additiona mixture of ethyl acetate and heptane (1:4) as eluent

Sources & evidence

ORD record
ord-17507e671104484bbf9cd7cd74beba97
Source dataset
uspto-grants-2000_06
Patent number
US06071901

Reaction notes

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