Potassium Carbonate → HCID 22469123, compound

HRID 1071243Notes

Reaction equation

HRID 1071243 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH:12]([OH:25])[CH2:13][CH2:14][C:15]1([C:21](OC)=[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:37]=[C:36]([F:38])[CH:35]=[C:34]([F:39])[CH:33]=1.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[CH:12]1[CH2:13][CH2:14][C:15]3([CH2:20][CH2:19][N:18]([CH2:29][CH2:30][O:31][C:32]4[CH:33]=[C:34]([F:39])[CH:35]=[C:36]([F:38])[CH:37]=4)[CH2:17][CH2:16]3)[C:21](=[O:22])[O:25]1)=[CH:9][C:8]([O:26][CH3:27])=[CH:7][CH:6]=2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 22247028HCID 22247028, compoundHCID 22469158HCID 22469158, compound

Product 1

HCID 22469123HCID 22469123, compoundYield 83.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 1 g of methyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)-3-(R,S)-hydroxypropyl]piperidine-4-carboxylate, 0.8 g of 1-(2-bromoethoxy)-3,5-difluorobenzene and 0.42 g of potassium carbonate in 45 cm3 of acetonitrile was maintained at a temperature of 80° C. with stirring and under an argon atmosphere for 20 hours. The suspension was filtered, the insoluble material was washed with ethyl acetate and the filtrate was then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue was purified by chromatography under a pressure of 100 kPa of argon, on a column of silica gel (particle size 40-60μ; diameter 3.5 cm; height: 38 cm), eluting with a dichloromethane/methanol mixture (97/4 by volume) and collecting 35-cm3 fractions. Fractions 9 to 20 were combined and then concentrated to dryness under the above conditions. 1.1 g of 3-(3-chloro-6-methoxyquinolin-4-yl)-9-[2-(3,5-difluorophenoxy)ethyl]-2-oxa-9-azaspiro[5.5]undecan-1-one were obtained.

Workup

  1. filtrationThe suspension was filtered
  2. washthe insoluble material was washed with ethyl acetate
  3. concentrationthe filtrate was then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
  4. customThe residue was purified by chromatography under a pressure of 100 kPa of argon, on a column of silica gel (particle size 40-60μ; diameter 3.5 cm; height: 38 cm)
  5. washeluting with a dichloromethane/methanol mixture (97/4 by volume)
  6. customcollecting 35-cm3 fractions
  7. concentrationconcentrated to dryness under the above conditions

Sources & evidence

ORD record
ord-691109043c0e48cb83c763971f7a093a
Source dataset
uspto-grants-2005_06
Patent number
US06903217B2

Reaction notes

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