Water → HCID 86586484, compound

HRID 394707Notes

Reaction equation

HRID 394707 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][CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH:16]1[CH2:21][C:22]([O-:24])=[O:23])=[CH:9][C:8]([O:25][CH3:26])=[CH:7][CH:6]=2.[C:27](=O)([O-])[O-].[K+].[K+].Br[CH2:34][CH2:35][S:36][C:37]1[S:38][CH:39]=[CH:40][CH:41]=1.O>CN(C)C=O.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH2:12][CH2:13][CH2:14][CH:15]1[CH2:20][CH2:19][N:18]([CH2:34][CH2:35][S:36][C:37]3[S:38][CH:39]=[CH:40][CH:41]=3)[CH2:17][CH:16]1[CH2:21][C:22]([O:24][CH3:27])=[O:23])=[CH:9][C:8]([O:25][CH3:26])=[CH:7][CH:6]=2

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 122011192-(2-Bromoethylthio)-thiopheneHCID 22643964HCID 22643964, compound

Product 1

HCID 86586484HCID 86586484, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A solution composed of 0.95 g of methyl (3RS,4RS) and (3SR,4RS)-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-3-acetate, 0.7 g of potassium carbonate, 0.68 g of 2-(2-bromoethylthio)thiophene in 40 cm3 of dimethylformamide was stirred for 16 hours at a temperature in the region of 60° C. under an inert atmosphere. After cooling to about 20° C., the reaction mixture was supplemented with 200 cm3 of water and 200 cm3 of ethyl acetate. The organic phase was separated after settling out and then washed 5 times with 100 cm3 of water and then with 100 cm3 of a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The evaporation residue obtained was purified by chromatography, under a nitrogen pressure of 50 kPa, on a column of silica gel (particle size 20-45 μ; diameter 2 cm; height 40 cm), eluting with a cyclohexane-ethyl acetate (68/32 by volume) mixture. 15-cm3 fractions were collected. Fractions 33 to 36 were concentrated. 195 mg of methyl (3SR,4RS)-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2-thienylthio)ethyl]piperidine-3-acetate were obtained in the form of an orange-colored oil.

Workup

  1. temperatureAfter cooling to about 20° C.
  2. customThe organic phase was separated
  3. washwashed 5 times with 100 cm3 of water
  4. dry with materialwith 100 cm3 of a saturated aqueous sodium chloride solution, dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  7. customThe evaporation residue obtained
  8. customwas purified by chromatography, under a nitrogen pressure of 50 kPa
  9. washon a column of silica gel (particle size 20-45 μ; diameter 2 cm; height 40 cm), eluting with a cyclohexane-ethyl acetate (68/32 by volume) mixture
  10. custom15-cm3 fractions were collected
  11. concentrationFractions 33 to 36 were concentrated

Sources & evidence

ORD record
ord-65d2e8861939490b9e3657af42240963
Source dataset
uspto-grants-2003_08
Patent number
US06602884B2

Reaction notes

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