Potassium Iodide → Ethyl 4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(3,4,5-trifluorophenoxy)ethyl]piperidine-4-carboxylate

HRID 1071271Notes

Reaction equation

HRID 1071271 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH2:12][CH2:13][CH2:14][C:15]1([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)=[CH:9][C:8]([O:26][CH3:27])=[CH:7][CH:6]=2.Br[CH2:29][CH2:30][O:31][C:32]1[CH:33]=[C:34]([F:40])[C:35]([F:39])=[C:36]([F:38])[CH:37]=1.[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH2:12][CH2:13][CH2:14][C:15]1([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:20][CH2:19][N:18]([CH2:29][CH2:30][O:31][C:32]3[CH:33]=[C:34]([F:40])[C:35]([F:39])=[C:36]([F:38])[CH:37]=3)[CH2:17][CH2:16]1)=[CH:9][C:8]([O:26][CH3:27])=[CH:7][CH:6]=2

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 22468445HCID 22468445, compoundHCID 224703895-(2-Bromoethoxy)-1,2,3-trifluorobenzene

Product 1

HCID 22469890Ethyl 4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(3,4,5-trifluorophenoxy)ethyl]piperidine-4-carboxylateYield 88.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 0.62 g of ethyl 4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate, 0.505 g of 5-(2-bromoethoxy)-1,2,3-trifluorobenzene, 0.34 g of potassium iodide and 1.14 g of potassium carbonate in 80 cm3 of acetonitrile was stirred under an inert atmosphere for 18 hours at a temperature in the region of 70° C. After cooling to about 20° C., the suspension was filtered and the insoluble material was washed with 3 times 30 cm3 of acetonitrile. The filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The evaporation residue was purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 20-45μ; diameter 3 cm; height 21 cm), eluting with ethyl acetate and collecting 40-cm3 fractions. Fractions 9 to 24 were combined and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 0.8 g of ethyl 4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(3,4,5-trifluorophenoxy)ethyl]piperidine-4-carboxylate was obtained in the form of a pale yellow viscous oil.

Workup

  1. temperatureAfter cooling to about 20° C.
  2. filtrationthe suspension was filtered
  3. washthe insoluble material was washed with 3 times 30 cm3 of acetonitrile
  4. concentrationThe filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
  5. customThe evaporation residue was purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 20-45μ; diameter 3 cm; height 21 cm)
  6. washeluting with ethyl acetate
  7. customcollecting 40-cm3 fractions
  8. concentrationconcentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-2dae5f118c3942f4bed2078dedde8b99
Source dataset
uspto-grants-2005_06
Patent number
US06903217B2

Reaction notes

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