Potassium Carbonate → HCID 53651881, compound

HRID 2226759Notes

Reaction equation

HRID 2226759 reaction equation
[CH:1]1[C:11]2[CH2:10][C:9]3[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=3[CH2:7][N:6]([CH2:16][CH2:17][O:18][CH2:19][CH2:20]O)[C:5]=2[CH:4]=[CH:3][CH:2]=1.CS(Cl)(=O)=O.C(=O)([O-])[O-].[K+].[K+].C(C(C(C(O)=O)O)O)(O)=O.[NH:43]1[CH2:48][CH2:47][CH2:46][C@@H:45]([C:49]([O:51][CH2:52][CH3:53])=[O:50])[CH2:44]1>C1(C)C=CC=CC=1.CC(CC(C)C)=O.C(OCC)(=O)C.CCCCCCC.O.C(N(CC)CC)C>[CH2:52]([O:51][C:49]([C@@H:45]1[CH2:46][CH2:47][CH2:48][N:43]([CH2:20][CH2:19][O:18][CH2:17][CH2:16][N:6]2[CH2:7][C:8]3[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=3[CH2:10][C:11]3[CH:1]=[CH:2][CH:3]=[CH:4][C:5]2=3)[CH2:44]1)=[O:50])[CH3:53]

Participants

11

Reactant 4

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 2733695(R)-(-)-Ethyl Nipecotate TartrateHCID 18965306HCID 18965306, compound

Product 1

HCID 53651881HCID 53651881, compoundYield 32%

Reagents, catalysts & solvents 6

HCID 962WaterSolvent2×HCID 1140TolueneSolvent2×HCID 7909Methyl Isobutyl KetoneSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolventHCID 8900HeptaneSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of the above alcohol (2.1 g, 7.4 mmol), triethylamine (2.6 ml) and toluene (30 ml) placed under an atmosphere of nitrogen was cooled on an ice-bath. A solution of methanesulfonyl chloride (2.1 g, 15 mmol) in toluene (5 ml) was added dropwise. Stirring was continued for 45 minutes on an ice-bath and then the temperature was allowed to reach ambient temperature. Water (20 ml) was added and the mixture was stirred at room temperature for 15 minutes. The phases were separated and the organic phases were washed with a 5% aqueous sodium bicarbonate solution and brine and dried over magnesium sulphate. The solvent was evaporated in vacuo to give an oil which was dissolved in methyl isobutylketone (40 ml). To this solution was added potassium carbonate (3.6 g, 26 mmol) and ethyl (R)-3-piperidinecarboxylate tartrate (4.6 g, 15 mmol). The suspension was heated at 40° C. for 24 h and then at reflux temperature for 3 h. The reaction mixture was allowed to cool to ambient temperature and water (50 ml) was added. The phases were separated and from the organic phase the solvent was evaporated in vacuo. This afforded an oily residue which was submitted to column chromatography on silica gel (125 g) using a mixture of ethyl acetate and n-heptane (1:1) as eluent. Collecting the proper fractions afforded 1.0 g of (R)-N-(2-(2-(6,11-dihydro-5H-dibenz[b,e]azepin-5-yl)ethoxy)ethyl)-3-piperidinecarboxylic acid ethyl ester as an oil. TLC: rf=0.36 (SiO2 ; ethyl acetate).

Workup

  1. temperaturewas cooled on an ice-bath
  2. customto reach ambient temperature
  3. stirringthe mixture was stirred at room temperature for 15 minutes
  4. customThe phases were separated
  5. washthe organic phases were washed with a 5% aqueous sodium bicarbonate solution and brine
  6. dry with materialdried over magnesium sulphate
  7. customThe solvent was evaporated in vacuo
  8. customto give an oil which
  9. temperatureat reflux temperature for 3 h
  10. temperatureto cool to ambient temperature
  11. customThe phases were separated and from the organic phase the solvent
  12. customwas evaporated in vacuo
  13. customThis afforded an oily residue which
  14. customCollecting the proper fractions

Sources & evidence

ORD record
ord-743b03bfa7dd4ab788cd92f6e9f9025e
Source dataset
uspto-grants-1994_09
Patent number
US05348965

Reaction notes

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