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

HRID 395003Notes

Reaction equation

HRID 395003 reaction equation
I[CH2:2][CH2:3][OH:4].C(=O)([O-])[O-].[K+].[K+].[F:11][C:12]1[CH:13]=[N:14][C:15]2[C:20]([C:21]=1[CH2:22][CH2:23][CH2:24][C:25]1([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1)=[CH:19][CH:18]=[CH:17][CH:16]=2>C(#N)C>[F:11][C:12]1[CH:13]=[N:14][C:15]2[C:20]([C:21]=1[CH2:22][CH2:23][CH2:24][C:25]1([C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:30][CH2:29][N:28]([CH2:2][CH2:3][OH:4])[CH2:27][CH2:26]1)=[CH:19][CH:18]=[CH:17][CH:16]=2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 12225IodoethanolHCID 22469283Ethyl 4-[3-(3-fluoroquinolin-4-yl)propyl]piperidine-4-carboxylate

Product 1

HCID 22468935Ethyl 4-[3-(3-fluoroquinolin-4-yl)-propyl]-1-(2-hydroxyethyl)piperidine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1.14 cm3 of 2-iodoethanol and 1.9 g of potassium carbonate were added to a solution of 4.4 g of ethyl 4-[3-(3-fluoroquinolin-4-yl)propyl]piperidine-4-carboxylate in 100 cm3 of anhydrous acetonitrile, with vigorous stirring and under an inert atmosphere. The reaction mixture was stirred for 18 hours in the region of 20° C., filtered and 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 50° C. The evaporation residue was purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 20-45μ; diameter 5 cm; height 32 cm), eluting with dichloromethane/methanol/aqueous ammonia (40/5/0.5 by volume) and collecting 100-cm3 fractions. Fractions 8 to 12 were combined and then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 3.5 g of ethyl 4-[3-(3-fluoroquinolin-4-yl)-propyl]-1-(2-hydroxyethyl)piperidine-4-carboxylate were obtained in the form of a viscous orange-colored oil.

Workup

  1. stirringThe reaction mixture was stirred for 18 hours in the region of 20° C.
  2. filtrationfiltered
  3. washwashed 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 50° C
  5. customThe evaporation residue was purified by chromatography under atmospheric pressure, on a column of silica gel (particle size 20-45μ; diameter 5 cm; height 32 cm)
  6. washeluting with dichloromethane/methanol/aqueous ammonia (40/5/0.5 by volume)
  7. customcollecting 100-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-408ce710ebda4e488b54b588ab83866d
Source dataset
uspto-grants-2003_08
Patent number
US06603005B2

Reaction notes

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