Sodium Hydroxide → (3Rs,4rs)-4-[3-(r,s)-amino-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2-thienylthio)ethyl]piperidine-3-acetic acid

HRID 394708Notes

Reaction equation

HRID 394708 reaction equation
[NH2:1][CH:2]([C:24]1[C:33]2[C:28](=[CH:29][CH:30]=[C:31]([O:34][CH3:35])[CH:32]=2)[N:27]=[CH:26][C:25]=1[F:36])[CH2:3][CH2:4][CH:5]1[CH2:10][CH2:9][N:8]([CH2:11][CH2:12][S:13][C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)[CH2:7][CH:6]1[CH2:19][C:20]([O:22]C)=[O:21].[OH-].[Na+].O1CCOCC1>O>[NH2:1][CH:2]([C:24]1[C:33]2[C:28](=[CH:29][CH:30]=[C:31]([O:34][CH3:35])[CH:32]=2)[N:27]=[CH:26][C:25]=1[F:36])[CH2:3][CH2:4][CH:5]1[CH2:10][CH2:9][N:8]([CH2:11][CH2:12][S:13][C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)[CH2:7][CH:6]1[CH2:19][C:20]([OH:22])=[O:21]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 131724009Methyl (3rs,4rs)-4-[3-(r,s)-amino-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2-thienylthio)ethyl]piperidine-3-acetate

Product 1

HCID 22643932(3Rs,4rs)-4-[3-(r,s)-amino-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2-thienylthio)ethyl]piperidine-3-acetic acidYield 68.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 0.355 g of methyl (3RS,4RS)-4-[3-(R,S)-amino-3-(3-fluoro-6methoxyquinolin-4-yl)propyl]-1-[2-(2-thienylthio)ethyl]piperidine-3-acetate in 1.66-cm3 of a 1 N aqueous sodium hydroxide solution and 5-cm of dioxane was heated at a temperature in the region of 60° C., with stirring, for 2 hours. After cooling to about 20° C., the reaction mixture was concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 50° C. The evaporation residue obtained was taken up in 30-cm3 of water and 30-cm3 of diethyl ether, the aqueous phase was separated after settling out and neutralized with 1.66-cm3 of a 1 N aqueous hydrochloric acid solution and was then extracted twice with 100-cm3 of ethyl acetate. The organic phase was dried over magnesium sulfate, filtered and then concentrated to dryness according to the same conditions above. 0.238 g of (3RS,4RS)-4-[3-(R,S)-amino-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2-thienylthio)ethyl]piperidine-3-acetic acid were obtained in the form of a white solid.

Workup

  1. temperatureAfter cooling to about 20° C.
  2. concentrationthe reaction mixture was concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 50° C
  3. customThe evaporation residue obtained
  4. custom30-cm3 of diethyl ether, the aqueous phase was separated
  5. extractionwas then extracted twice with 100-cm3 of ethyl acetate
  6. dry with materialThe organic phase was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-861dfb17f1ca44308548972c6a09f7bd
Source dataset
uspto-grants-2003_08
Patent number
US06602884B2

Reaction notes

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