Potassium Iodide → HCID 86758165, compound

HRID 2186387Notes

Reaction equation

HRID 2186387 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].C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Cl[CH2:37][CH2:38][S:39][C:40]1[CH:45]=[CH:44][CH:43]=[C:42]([F:46])[CH:41]=1>C(#N)C.O>[F:46][C:42]1[CH:41]=[C:40]([S:39][CH2:38][CH2:37][N:8]2[CH2:9][CH2:10][C@@H:5]([CH2:4][CH2:3][C:2](=[O:1])[C:16]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH3:27])[CH:24]=4)[N:19]=[CH:18][CH:17]=3)[C@@H:6]([CH2:11][C:12]([O:14][CH3:15])=[O:13])[CH2:7]2)[CH:45]=[CH:44][CH:43]=1

Participants

7

Reactant 4

HCID 4875Potassium Iodide2×HCID 11430Potassium CarbonateHCID 22453101HCID 22453101, compoundHCID 70173611HCID 70173611, compound

Product 1

HCID 86758165HCID 86758165, compoundYield 103.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
20 °C

Procedure

2.26 g of methyl(3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-acetate, dissolved beforehand in 50 cm3 of acetonitrile, were added dropwise, with stirring and at a temperature in the region of 20° C., followed by 6.91 g of potassium carbonate and 2 g of potassium iodide, to a solution of 4 g of 1-[(2-chloroethyl)thio]-3-fluorobenzene in 50 cm3 of acetonitrile. The mixture was heated for 18 hours at a temperature in the region of 70° C. After a further addition of 0.3 g of potassium iodide and additional heating at a temperature in the region of 70° C. for 4 hours, the reaction mass was cooled to approximately 20° C., 200 cm3 of water were added and extraction was carried out with 2 times 150 cm3 of ethyl acetate. The combined extracts were washed with 300 cm3 of water, dried over magnesium sulfate, filtered, and evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained was purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45 μ; diameter 5.2 cm; silica volume 950 cm3), elution was carried out with a dichloromethane/methanol (99/1 by volume) mixture, and approximately 6-cm3 fractions were collected. Fractions 24 to 36 were combined and concentrated under the above conditions. 3.3 g of methyl (3R,4R)-1-[2-(3-fluorophenylthio)ethyl]-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-acetate were obtained in the form of an oil with a yellow color.

Workup

  1. additionwere added dropwise
  2. temperatureThe mixture was heated for 18 hours at a temperature in the region of 70° C
  3. temperatureadditional heating at a temperature in the region of 70° C. for 4 hours
  4. temperaturethe reaction mass was cooled to approximately 20° C.
  5. extractionextraction
  6. washThe combined extracts were washed with 300 cm3 of water
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customevaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  10. customThe residue obtained
  11. customwas purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45 μ; diameter 5.2 cm; silica volume 950 cm3), elution
  12. customwere collected
  13. concentrationconcentrated under the above conditions

Sources & evidence

ORD record
ord-1a6d7d533b91411ead06b16686f7bddb
Source dataset
uspto-grants-2002_06
Patent number
US06403610B1

Reaction notes

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