Potassium Iodide → Ethyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-1-(2-(cyclopentylthio)ethyl]piperidine-4-carboxylate

HRID 394977Notes

Reaction equation

HRID 394977 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH2:12][CH2:13][CH2:14][C:15]1([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)=[CH:9][C:8]([O:26][CH3:27])=[CH:7][CH:6]=2.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Cl[CH2:37][CH2:38][S:39][CH:40]1[CH2:44][CH2:43][CH2:42][CH2:41]1>C(#N)C>[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH2:12][CH2:13][CH2:14][C:15]1([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:20][CH2:19][N:18]([CH2:37][CH2:38][S:39][CH:40]3[CH2:44][CH2:43][CH2:42][CH2:41]3)[CH2:17][CH2:16]1)=[CH:9][C:8]([O:26][CH3:27])=[CH:7][CH:6]=2

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 22468602HCID 22468602, compoundHCID 22468654(2-Chloroethylthio)cyclopentane

Product 1

HCID 22468662Ethyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-1-(2-(cyclopentylthio)ethyl]piperidine-4-carboxylateYield 56.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

1.2 g of ethyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate, 0.51 g of potassium carbonate and 0.61 g of potassium iodide were added, at a temperature in the region of 20° C., with stirring and under an inert atmosphere, to a solution of 0.607 g of (2-chloroethylthio)cyclopentane in 50 cm3 of acetonitrile. After heating for 20 hours at a temperature in the region of 80° C., the reaction mixture was cooled to about 20° C., filtered and concentrated under reduced pressure (1 kPa) at a temperature in the region of 50° C. The residue obtained was purified by chromatography under a nitrogen pressure of 100 kPa, on a column of silica gel (particle size 40-60μ; diameter 3.5 cm), eluting with a mixture of dichloromethane/methanol (98/2 by volume) and collecting 35-cm3 fractions. Fractions 25 to 31 were combined and then concentrated as above. 0.9 g of ethyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-1-[2-(cyclopentylthio)ethyl]piperidine-4-carboxylate was obtained.

Workup

  1. temperaturethe reaction mixture was cooled to about 20° C.
  2. filtrationfiltered
  3. concentrationconcentrated under reduced pressure (1 kPa) at a temperature in the region of 50° 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 40-60μ; diameter 3.5 cm), eluting with a mixture of dichloromethane/methanol (98/2 by volume)
  7. customcollecting 35-cm3 fractions
  8. concentrationconcentrated as above

Sources & evidence

ORD record
ord-815f6bedd83e4617a8995ef3f68057d7
Source dataset
uspto-grants-2003_08
Patent number
US06603005B2

Reaction notes

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