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

HRID 2186364Notes

Reaction equation

HRID 2186364 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].[C:27]([S:31][CH2:32][CH2:33]Cl)([CH3:30])([CH3:29])[CH3:28].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]([CH2:33][CH2:32][S:31][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:7][C@@H:6]1[C:11]([O:13][CH3:14])=[O:12]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 962622-((2-Chloroethyl)thio)-2-methylpropaneHCID 66688355HCID 66688355, compound

Product 1

HCID 131723276methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(tert-butylthio)ethyl]piperidine-3-carboxylateYield 27.9%

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 16 hours at a temperature in the region of the reflux temperature, with stirring and under an inert atmosphere, with 0.43 g of 2-chloroethyl tert-butyl sulfide in the presence of 0.33 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. 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 35 cm), elution being was out with a dichloromethane/methanol (97/3 by volume) mixture, and 35-cm3 fractions were collected. Fractions 54 to 70 were combined and then evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C. 0.265 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(tert-butylthio)ethyl]piperidine-3-carboxylate was obtained in the form of a lacquer with a brown color.

Workup

  1. filtrationthe insoluble material was filtered off
  2. customThe filtrate was evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  3. customThe residue obtained
  4. customwas purified by chromatography under a nitrogen pressure of 100 kPa
  5. washon a column of silica gel (particle size 40-63 μm; diameter 3.5 cm; height 35 cm), elution being
  6. customwere collected
  7. customevaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-72009bababca434b9a34207b727e8bba
Source dataset
uspto-grants-2002_06
Patent number
US06403610B1

Reaction notes

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