Sodium Hydroxide → HCID 10459358, compound

HRID 1760232Notes

Reaction equation

HRID 1760232 reaction equation
[OH-].[Na+].[OH:3][CH:4]([C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([O:35][CH3:36])[CH:33]=2)[N:28]=[CH:27][C:26]=1[Cl:37])[CH2:5][CH2:6][CH:7]1[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][S:15][C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)[CH2:9][CH:8]1[C:21]([O:23]C)=[O:22]>O1CCOCC1>[OH:3][CH:4]([C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([O:35][CH3:36])[CH:33]=2)[N:28]=[CH:27][C:26]=1[Cl:37])[CH2:5][CH2:6][CH:7]1[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][S:15][C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)[CH2:9][CH:8]1[C:21]([OH:23])=[O:22]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 12114749HCID 12114749, compound

Product 1

HCID 10459358HCID 10459358, compoundYield 82.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

Stereoisomer D 1.8 cm3 of a 1 N aqueous sodium hydroxide solution are added to 325 mg of methyl 4-[3-hydroxy-3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2-thienylsulfanyl)ethyl]piperidine-3-carboxylate (ester isomer D) solubilized in 10 cm3 of dioxane. The reaction medium is then heated at 70° C. for 5 h 30 min. The temperature is allowed to return to 19° C. for 12 hours and then heating is carried out again at 70° C. for 2 hours. Evaporation is then carried out under reduced pressure (20 kPa; 45° C.). The residue is taken up in 25 cm3 of distilled water and then extraction is carried out with 25 cm3 of diethyl ether. The aqueous phase is acidified with 1.6 cm3 of a 1 N aqueous hydrochloric acid solution (pH=6) and then this phase is extracted with 3 times 70 cm3 of ethyl acetate. The organic phase is dried under magnesium sulfate, filtered through a sintered glass funnel, and then evaporated under reduced pressure (20 kPa; 45° C.). After having dried under vacuum (50 kPa), the residue is taken up with 20 cm3 of acetone and then concentrated again under reduced pressure (20 kPa; 45° C.). Drying is carried out under reduced pressure (50 kPa; 20° C.) for 12 hours and 260 mg of 4-[3-hydroxy-3-(3-chloro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2-thienylsulfanyl)ethyl]piperidine-3-carboxylic acid, in the form of a pale yellow solid (isomer D), are obtained.

Workup

  1. temperatureheating
  2. waitis carried out again at 70° C. for 2 hours
  3. customEvaporation
  4. customis then carried out under reduced pressure (20 kPa; 45° C.)
  5. extractionextraction
  6. extractionthis phase is extracted with 3 times 70 cm3 of ethyl acetate
  7. customThe organic phase is dried under magnesium sulfate
  8. filtrationfiltered through a sintered glass funnel
  9. customevaporated under reduced pressure (20 kPa; 45° C.)
  10. customAfter having dried under vacuum (50 kPa)
  11. concentrationconcentrated again under reduced pressure (20 kPa; 45° C.)
  12. customDrying
  13. waitis carried out under reduced pressure (50 kPa; 20° C.) for 12 hours

Sources & evidence

ORD record
ord-81377055d016489288d12267a43e314f
Source dataset
uspto-grants-2005_01
Patent number
US06841562B2

Reaction notes

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