Potassium Iodide → methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(5-chlorothien-2-yl)ethyl]piperidine-3-carboxylate

HRID 2186376Notes

Reaction equation

HRID 2186376 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(=O)([O-])[O-].[K+].[K+].[I-].[K+].[Cl:35][C:36]1[S:37][C:38](SCCCl)=[CH:39][CH:40]=1.[C:45](#N)[CH3:46]>CO.C(OCC)(=O)C>[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]([CH2:45][CH2:46][C:38]2[S:37][C:36]([Cl:35])=[CH:40][CH:39]=2)[CH2:7][C@@H:6]1[C:11]([O:13][CH3:14])=[O:12]

Participants

8

Reactant 5

HCID 4875Potassium IodideHCID 6342Acetonitrile2×HCID 11430Potassium CarbonateHCID 224535192-Chloro-5-(2-chloroethylthio)thiopheneHCID 66688355HCID 66688355, compound

Product 1

HCID 131723280methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(5-chlorothien-2-yl)ethyl]piperidine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 1 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate in 40 cm3 of acetonitrile and 10 cm3 of methanol was stirred at a temperature. in the region of 20° C. and then 1.16 g of potassium carbonate and 0.5 g of potassium iodide were added. 1 g of 2-chloro-5-(2-chloroethylthio)thiophene and 10 cm3 of acetonitrile were added to the suspension obtained. The mixture was stirred for 72 hours at a temperature in the region of 80° C. The reaction mass was poured onto 75 cm3 of ethyl acetate and then washed with 3 times 70 cm3 of water. The organic phase was dried over sodium sulfate, filtered, and evaporated under reduced pressure (5 kPa) at a temperature in the region of 45° C. The residue obtained was purified by chromatography under a nitrogen pressure of 40 kPa on a column of silica gel (particle size 20-40 μm; diameter 3.5 cm; silica height 31 cm), elution was carried out with ethyl acetate, and 30-cm3 fractions were collected. Fractions 24 to 52 were combined and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. 0.48 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(5-chlorothien-2-yl)ethyl]piperidine-3-carboxylate was obtained in the form of an oil with a brown color.

Workup

  1. customobtained
  2. washwashed with 3 times 70 cm3 of water
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated under reduced pressure (5 kPa) at a temperature in the region of 45° C
  6. customThe residue obtained
  7. customwas purified by chromatography under a nitrogen pressure of 40 kPa
  8. washon a column of silica gel (particle size 20-40 μm; diameter 3.5 cm; silica height 31 cm), elution
  9. customwere collected
  10. concentrationconcentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-61fc0c3fe2b3472f8744bcbf3072b845
Source dataset
uspto-grants-2002_06
Patent number
US06403610B1

Reaction notes

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