Potassium Carbonate → HCID 11827083, compound

HRID 2226766Notes

Reaction equation

HRID 2226766 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:11][CH2:10][C:9]3[CH:12]=[CH:13][C:14]([Cl:16])=[CH:15][C:8]=3[N:7]([CH2:17][CH2:18][O:19][CH2:20][CH2:21]O)[C:6]=2[CH:23]=1.CS(Cl)(=O)=O.C(=O)([O-])[O-].[K+].[K+].[NH:35]1[CH2:40][CH2:39][CH2:38][C@@H:37]([C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:36]1>C(OCC)C.CC(C)=O.C(OCC)(=O)C.CCCCCCC.C(N(CC)CC)C>[CH2:44]([O:43][C:41]([C@@H:37]1[CH2:38][CH2:39][CH2:40][N:35]([CH2:21][CH2:20][O:19][CH2:18][CH2:17][N:7]2[C:6]3[CH:23]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=3[CH2:11][CH2:10][C:9]3[CH:12]=[CH:13][C:14]([Cl:16])=[CH:15][C:8]2=3)[CH2:36]1)=[O:42])[CH3:45]

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 185582ethyl (3R)-piperidine-3-carboxylate2×HCID 11727873HCID 11727873, compound

Product 1

HCID 11827083HCID 11827083, compoundYield 82.5%

Reagents, catalysts & solvents 5

HCID 180AcetoneSolventHCID 3283Diethyl EtherSolvent2×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolventHCID 8900HeptaneSolvent

Procedure

To a mixture of the above alcohol (1.3 g, 3.7 mmol), triethylamine (1.3 ml) and dry diethyl ether (75 ml) was added dropwise a solution of methanesulfonyl chloride (0.63 g, 5.5 mmol) in dry diethyl ether (25 ml). Stirring was continued for 1 h at room temperature. The reaction mixture was washed with water and dried over potassium carbonate. The solvent was evaporated in vacuo to give an oily residue which was dissolved in acetone (30 ml). To this solution was added potassium carbonate (1.0 g, 7.4 mmol) and ethyl (R)-3-piperidinecarboxylate (1.2 g, 7.4 mmol) and the suspension was heated at reflux temperature for 16 h. Another portion of ethyl (R)-3-piperidinecarboxylate (0.5 g) was added and the mixture was heated at reflux temperature for 24 h. This cooled reaction mixture was filtered and from the filtrate the solvent was evaporated in vacuo. This afforded an oil which was submitted to column chromatography on silica gel (100 g) using a mixture of ethyl acetate and n-heptane (1:1) as eluent. Collecting the proper fractions gave 1.5 g of (R)-N-(2-(2-(3,7-dichloro-10,11-dihydro-5H-dibenz[b,f]-azepin-5-yl)ethoxy)ethyl)-3-piperidinecarboxylic acid ethyl ester as an oil. TLC: rf=0.18 (SiO2 ; ethyl acetate/n-heptane=1:1 ).

Workup

  1. washThe reaction mixture was washed with water
  2. dry with materialdried over potassium carbonate
  3. customThe solvent was evaporated in vacuo
  4. customto give an oily residue which
  5. temperaturethe suspension was heated
  6. temperatureat reflux temperature for 16 h
  7. temperaturethe mixture was heated
  8. temperatureat reflux temperature for 24 h
  9. customThis cooled reaction mixture
  10. filtrationwas filtered and from the filtrate the solvent
  11. customwas evaporated in vacuo
  12. customThis afforded an oil which
  13. customCollecting the proper fractions

Sources & evidence

ORD record
ord-2dd251bfef45406ab16e49184412612a
Source dataset
uspto-grants-1994_09
Patent number
US05348965

Reaction notes

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