Potassium Carbonate → Ethyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-1-(2-hydroxyethyl)piperidine-4-carboxylate

HRID 394981Notes

Reaction equation

HRID 394981 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][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.C(=O)([O-])[O-].[K+].[K+].I[CH2:35][CH2:36][OH:37]>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][CH3:25])=[O:22])[CH2:20][CH2:19][N:18]([CH2:35][CH2:36][OH:37])[CH2:17][CH2:16]1)=[CH:9][C:8]([O:26][CH3:27])=[CH:7][CH:6]=2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 12225Iodoethanol2×HCID 22468602HCID 22468602, compound

Product 1

HCID 22469057Ethyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-1-(2-hydroxyethyl)piperidine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

3.9 g of ethyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]piperidine-4-carboxylate and 2.07 g of potassium carbonate were added to a solution of 1.17 cm3 of 2-iodoethanol in 80 cm3 of acetonitrile, at a temperature in the region of 20° C. with stirring and under an inert atmosphere. After heating for 23 hours at a temperature in the region of 80° C., a further 1.17 cm3 of 2-iodoethanol were added. After heating for 40 hours at a temperature in the region of 80° C., the reaction mixture was cooled to about 20° C., filtered and concentrated under reduced pressure (1 kPa) at a temperature in the region of 50° C. The residue obtained was purified by chromatography under a pressure of 100 kPa of nitrogen, on a column of silica gel (particle size 40-60μ; diameter 4 cm; height 60 cm), eluting with a dichloromethane/methanol/aqueous ammonia mixture (89/10/1 by volume) and collecting 50-cm3 fractions. Fractions 14 to 17 were combined and then concentrated as previously. 1.9 g of ethyl 4-[3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-1-(2-hydroxyethyl)piperidine-4-carboxylate were obtained.

Workup

  1. temperatureAfter heating for 40 hours at a temperature in the region of 80° C.
  2. temperaturethe reaction mixture was cooled to about 20° C.
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure (1 kPa) at a temperature in the region of 50° C
  5. customThe residue obtained
  6. customwas purified by chromatography under a pressure of 100 kPa of nitrogen, on a column of silica gel (particle size 40-60μ; diameter 4 cm; height 60 cm)
  7. washeluting with a dichloromethane/methanol/aqueous ammonia mixture (89/10/1 by volume)
  8. customcollecting 50-cm3 fractions
  9. concentrationconcentrated as previously

Sources & evidence

ORD record
ord-f43525a238a441dbac0f0531251536e3
Source dataset
uspto-grants-2003_08
Patent number
US06603005B2

Reaction notes

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