Potassium Iodide → HCID 22469149, compound

HRID 394979Notes

Reaction equation

HRID 394979 reaction equation
[Cl: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][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:22])[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)=[CH:9][C:8]([O:31][CH3:32])=[CH:7][CH:6]=2.Br[CH2:34][CH2:35][O:36][C:37]1[C:42]([F:43])=[CH:41][CH:40]=[CH:39][C:38]=1[F:44].[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Cl: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][C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)=[O:22])[CH2:20][CH2:19][N:18]([CH2:34][CH2:35][O:36][C:37]3[C:38]([F:44])=[CH:39][CH:40]=[CH:41][C:42]=3[F:43])[CH2:17][CH2:16]1)=[CH:9][C:8]([O:31][CH3:32])=[CH:7][CH:6]=2

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 22468465HCID 22468465, compoundHCID 22470635HCID 22470635, compound

Product 1

HCID 22469149HCID 22469149, compoundYield 87.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 1.4 g of benzyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate, 0.82 g of 1-(2-bromoethoxy)-2,6-difluorobenzene, 0.6 g of potassium iodide and 2 g of potassium carbonate in 100 cm3 of acetonitrile was heated for 18 hours at a temperature in the region of 75° C., with stirring and under an inert atmosphere. After cooling to a temperature in the region of 20° C., the reaction mixture was filtered and washed with three 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 residue obtained was purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 20-45μ; diameter 3 cm; height: 27 cm), eluting with ethyl acetate and collecting 50-cm3 fractions. Fractions 7 to 17 were combined and then concentrated to dryness under the above conditions. 1.65 g of benzyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,6-difluorophenoxy)ethyl]piperidine-4-carboxylate were obtained in the form of a thick yellow oil.

Workup

  1. temperatureAfter cooling to a temperature in the region of 20° C.
  2. filtrationthe reaction mixture was filtered
  3. washwashed with three 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 residue obtained
  6. customwas purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 20-45μ; diameter 3 cm; height: 27 cm)
  7. washeluting with ethyl acetate
  8. customcollecting 50-cm3 fractions
  9. concentrationconcentrated to dryness under the above conditions

Sources & evidence

ORD record
ord-4a533da312f14c6faa69e61e997db1b5
Source dataset
uspto-grants-2003_08
Patent number
US06603005B2

Reaction notes

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