Water → methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin4-yl)propyl]-1-[2-(cyclopentylthio)ethyl]piperidine-3-acetate

HRID 2186399Notes

Reaction equation

HRID 2186399 reaction equation
[BH4-].[Na+].[O:3]=[C:4]([C:26]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([O:36][CH3:37])[CH:34]=2)[N:29]=[CH:28][CH:27]=1)[CH2:5][CH2:6][C@@H:7]1[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][S:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:9][C@@H:8]1[CH2:21][C:22]([O:24][CH3:25])=[O:23].O>CO.[OH-].[Na+]>[OH:3][CH:4]([C:26]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([O:36][CH3:37])[CH:34]=2)[N:29]=[CH:28][CH:27]=1)[CH2:5][CH2:6][C@@H:7]1[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][S:15][CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:9][C@@H:8]1[CH2:21][C:22]([O:24][CH3:25])=[O:23]

Participants

6

Reactant 3

HCID 962WaterHCID 4311764Sodium borohydrideHCID 86758169methyl (3R,4R)-4-(3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(cyclopentylthio)ethyl]piperidine-3-acetate

Product 1

HCID 131723292methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin4-yl)propyl]-1-[2-(cyclopentylthio)ethyl]piperidine-3-acetateYield 83.7%

Reagents, catalysts & solvents 2

HCID 14798Sodium HydroxideCatalystHCID 887MethanolSolvent

Procedure

0.227 g of sodium borohydride was added portionwise over approximately 30 minutes at a temperature of less than 30° C., with stirring and under an inert atmosphere, to a mixture of 2.5 g of methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(cyclopentylthio)ethyl]piperidine-3-acetate in 40 cm3 of methanol to which had been added one drop of 5N aqueous sodium hydroxide solution. After stirring the reaction mixture for 3 hours at a temperature in the region of 20° C., 100 cm3 of water were added and then the mixture was extracted with 4 times 50 cm3 of ethyl acetate. The combined extracts were washed with 3 times 50 cm3 of water, dried over magnesium sulfate, filtered, and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residual oil obtained was purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45 μm; diameter 3.2 cm; silica volume 100 cm3), elution was carried out with pure ethyl acetate, and 25-cm3 fractions were collected. The fractions comprising the expected product were combined and then concentrated as above. 2.1 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin4-yl)propyl]-1-[2-(cyclopentylthio)ethyl]piperidine-3-acetate were obtained in the form of an oil with a pale yellow color. The hydrochloride was prepared in the following way: a solution of 0.5 g of the oil obtained above, dissolved in 15 cm3 of dichloromethane, was poured with stirring into 4 cm3 of a 1N solution of hydrochloric acid in diethyl ether. A product precipitated and then crystallized by addition of 25 cm3 of diethyl ether. The solid was filtered off, washed with 2 times 10 cm3 of ether, and dried under vacuum over potassium hydroxide (5 kPa) and then, to constant weight, in an oven under reduced pressure (10 Pa) at a temperature in the region of 40° C. 0.35 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[2-(cyclopentylthio)ethyl]piperidine-3-acetate dihydrochloride was obtained in the form of a solid with an off-white color.

Workup

  1. additionwere added
  2. extractionthe mixture was extracted with 4 times 50 cm3 of ethyl acetate
  3. washThe combined extracts were washed with 3 times 50 cm3 of water
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  7. customThe residual oil obtained
  8. customwas purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45 μm; diameter 3.2 cm; silica volume 100 cm3), elution
  9. customwere collected
  10. concentrationconcentrated as above

Sources & evidence

ORD record
ord-d0b9deca09dd459e809567a291d673d3
Source dataset
uspto-grants-2002_06
Patent number
US06403610B1

Reaction notes

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