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

HRID 2186374Notes

Reaction equation

HRID 2186374 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:33][CH2:34][CH2:35]Cl)[CH2:32][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]([CH2:35][CH2:34][S:33][CH:27]2[CH2:32][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 22469748[(2-Chloroethyl)sulfanyl]cyclohexaneHCID 66688355HCID 66688355, compound

Product 1

HCID 131723279methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(cyclohexylthio)ethyl]piperidine-3-carboxylateYield 53%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Procedure

A stirred mixture of 0.54 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate, 0.295 g of 2-chloroethyl cyclohexyl sulfide, 0.23 g of potassium carbonate, and 0.27 g of potassium iodide in 9 cm3 of acetonitrile and 1 cm3 of methanol was brought to a temperature in the region of the boiling point under an inert atmosphere for 20 hours. The reaction mixture was concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained was purified by chromatography under an argon pressure of 80 kPa on a column of silica gel (particle size 40-63 μm; diameter 3.5 cm; height 35 cm), elution was carried out with a dichloromethane/methanol (95/5 by volume) mixture, and 35-cm3 fractions were collected. Fractions 23 to 40 were combined and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. 0.4 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(cyclohexylthio)ethyl]piperidine-3-carboxylate was obtained in the form of a lacquer with a brown color.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  2. customThe residue obtained
  3. customwas purified by chromatography under an argon pressure of 80 kPa
  4. washon a column of silica gel (particle size 40-63 μm; diameter 3.5 cm; height 35 cm), elution
  5. customwere collected
  6. concentrationconcentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-8c4b7a48a6a944b0945f4a62c7b47cfe
Source dataset
uspto-grants-2002_06
Patent number
US06403610B1

Reaction notes

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