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

HRID 2186400Notes

Reaction equation

HRID 2186400 reaction equation
[O:1]=[C:2]([C:16]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH3:27])[CH:24]=2)[N:19]=[CH:18][CH:17]=1)[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][NH:8][CH2:7][C@@H:6]1[CH2:11][C:12]([O:14][CH3:15])=[O:13].[CH:28]1([S:33][CH2:34][CH2:35]Cl)[CH2:32][CH2:31][CH2:30][CH2:29]1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>C(#N)C.O>[O:1]=[C:2]([C:16]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH3:27])[CH:24]=2)[N:19]=[CH:18][CH:17]=1)[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][N:8]([CH2:35][CH2:34][S:33][CH:28]2[CH2:32][CH2:31][CH2:30][CH2:29]2)[CH2:7][C@@H:6]1[CH2:11][C:12]([O:14][CH3:15])=[O:13]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 22468654(2-Chloroethylthio)cyclopentaneHCID 70173611HCID 70173611, compound

Product 1

HCID 86758169methyl (3R,4R)-4-(3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(cyclopentylthio)ethyl]piperidine-3-acetateYield 39.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 4.9 g of methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-acetate, 2.9 g of 2-chloroethyl cyclopentyl sulfide, 9 g of potassium carbonate, and 2.7 g of potassium iodide in 130 cm3 of acetonitrile was stirred for 17 hours at a temperature in the region of 65° C. After cooling to a temperature in the region of 20° C., the reaction mixture has 150 cm3 of water added and was extracted with 3 times 60 cm3 of ethyl acetate. The organic extracts were combined, washed with 2 times 50 cm3, dried over magnesium sulfate, filtered, and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. An oil was obtained, which product was purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45 μm; diameter 4 cm; silica volume 300 cm3), elution was carried out with pure ethyl acetate, and approximately 70-cm3 fractions were collected. The fractions comprising the expected product were combined and then concentrated under the above conditions. 2.6 g of methyl (3R,4R)-4-(3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(cyclopentylthio)ethyl]piperidine-3-acetate were obtained in the form of an oil with a yellow color.

Workup

  1. temperatureAfter cooling to a temperature in the region of 20° C.
  2. additionadded
  3. extractionwas extracted with 3 times 60 cm3 of ethyl acetate
  4. washwashed with 2 times 50 cm3
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  8. customAn oil was obtained
  9. customwhich product was purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45 μm; diameter 4 cm; silica volume 300 cm3), elution
  10. customwere collected
  11. concentrationconcentrated under the above conditions

Sources & evidence

ORD record
ord-ed2314a3c32c412db2a16d1e75eaad57
Source dataset
uspto-grants-2002_06
Patent number
US06403610B1

Reaction notes

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