Hydrochloric Acid → methyl (3R,4R)-4-[3-oxo-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate

HRID 1767092Notes

Reaction equation

HRID 1767092 reaction equation
Cl.C(OC([N:9]1[CH2:14][CH2:13][C@@H:12]([CH2:15][CH2:16][C:17]([C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[C:26]([O:29][CH3:30])[CH:27]=3)[N:22]=[CH:21][C:20]=2[F:31])=[O:18])[C@@H:11]([C:32]([O:34][CH3:35])=[O:33])[CH2:10]1)=O)(C)(C)C.[OH-].[Na+]>C(OCC)(=O)C.CO>[F:31][C:20]1[CH:21]=[N:22][C:23]2[C:28]([C:19]=1[C:17](=[O:18])[CH2:16][CH2:15][C@@H:12]1[CH2:13][CH2:14][NH:9][CH2:10][C@@H:11]1[C:32]([O:34][CH3:35])=[O:33])=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 86592160methyl (3R,4R)-1-tert-butyloxycarbonyl-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)-3-oxopropyl]piperidine-3-carboxylate

Product 1

HCID 11501661methyl (3R,4R)-4-[3-oxo-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylateYield 86.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent3×

Conditions

Temperature
20 °C

Procedure

9 cm3 of a 4N solution of hydrochloric acid in ethyl acetate and 10 cm3 of MeOH are added, at a temperature in the region of 20° C., to 4 g (7.23 mmol) of methyl (3R,4R)-1-tert-butyloxycarbonyl-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)-3-oxopropyl]piperidine-3-carboxylate in solution in 20 cm3 of ethyl acetate. After stirring for 4 hours at a temperature in the region of 20° C., the reaction mixture is diluted with 25 cm3 of ethyl acetate and a 5N aqueous sodium hydroxide solution is then added in order to adjust the pH of the aqueous phase to a value of between 8 and 8.5. The organic phase is separated after settling out and the aqueous phase is then extracted with 3 times 40 cm3 of ethyl acetate. The organic phases are pooled, washed with 2 times 50 cm3 of a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and concentrated to dryness under reduced pressure (2.7 kPa) to give 2.33 g of methyl (3R,4R)-4-[3-(3-fluoro-6-methoxyquinolin-4-yl)-3-oxopropyl]-piperidine-3-carboxylate in the form of an orange oil.

Workup

  1. customThe organic phase is separated
  2. extractionthe aqueous phase is then extracted with 3 times 40 cm3 of ethyl acetate
  3. washwashed with 2 times 50 cm3 of a saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-f5c3981999c84b2e82ad29cd0805f2f8
Source dataset
uspto-grants-2007_06
Patent number
US07232834B2

Reaction notes

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