Potassium Iodide → methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(cyclopentylthio)-ethyl]piperidine-3-carboxylate

HRID 2186366Notes

Reaction equation

HRID 2186366 reaction equation
[OH:1][CH:2]([C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([O:25][CH3:26])[CH:23]=2)[N:18]=[CH:17][CH:16]=1)[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][NH:8][CH2:7][C@@H:6]1[C:11]([O:13][CH3:14])=[O:12].[CH:27]1([S:32][CH2:33][CH2:34]Cl)[CH2:31][CH2:30][CH2:29][CH2:28]1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>C(#N)C.CO>[OH:1][CH:2]([C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([O:25][CH3:26])[CH:23]=2)[N:18]=[CH:17][CH:16]=1)[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][N:8]([CH2:34][CH2:33][S:32][CH:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)[CH2:7][C@@H:6]1[C:11]([O:13][CH3:14])=[O:12]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 22468654(2-Chloroethylthio)cyclopentaneHCID 66688355HCID 66688355, compound

Product 1

HCID 131723277methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(cyclopentylthio)-ethyl]piperidine-3-carboxylateYield 49.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
20 °C

Procedure

0.717 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate in 15 cm3 of acetonitrile and 15 cm3 of methanol was heated for 3½ h at a temperature in the region of the reflux temperature, with stirring and under an inert atmosphere, with 0.439 g of 90% 2-chloroethyl cyclopentyl sulfide in the presence of 0.332 g of potassium carbonate and 0.4 g of potassium iodide. After cooling the reaction mixture to a temperature in the region of 20° C., the insoluble material was filtered off and then washed with acetonitrile. The filtrate was evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained was purified by chromatography under a nitrogen pressure of 100 kPa on a column of silica gel (particle size 40-63 μm; diameter 3.5 cm; height 45 cm), elution was carried out with a dichloromethane/methanol (95/5 by volume) mixture, and 35-cm3 fractions were collected. Fractions 25 to 45 were combined and then evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C. 0.48 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(cyclopentylthio)-ethyl]piperidine-3-carboxylate was obtained in the form of a lacquer with a dark-green color.

Workup

  1. filtrationthe insoluble material was filtered off
  2. washwashed with acetonitrile
  3. customThe filtrate was evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  4. customThe residue obtained
  5. customwas purified by chromatography under a nitrogen pressure of 100 kPa
  6. washon a column of silica gel (particle size 40-63 μm; diameter 3.5 cm; height 45 cm), elution
  7. customwere collected
  8. customevaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-edafad926e04463b8e8fd9778671932e
Source dataset
uspto-grants-2002_06
Patent number
US06403610B1

Reaction notes

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