Hydroxyamine hydrochloride → methyl (3R,4R)-1-[2-(thien-2-ylthio)ethyl]-4-[3-hydroxyimino-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate

HRID 393223Notes

Reaction equation

HRID 393223 reaction equation
Cl.[NH2:2][OH:3].[S:4]1[CH:8]=[CH:7][CH:6]=[C:5]1[S:9][CH2:10][CH2:11][N:12]1[CH2:17][CH2:16][C@@H:15]([CH2:18][CH2:19][C:20](=O)[C:21]2[C:30]3[C:25](=[CH:26][CH:27]=[C:28]([O:31][CH3:32])[CH:29]=3)[N:24]=[CH:23][CH:22]=2)[C@@H:14]([C:34]([O:36][CH3:37])=[O:35])[CH2:13]1>N1C=CC=CC=1.O>[S:4]1[CH:8]=[CH:7][CH:6]=[C:5]1[S:9][CH2:10][CH2:11][N:12]1[CH2:17][CH2:16][C@@H:15]([CH2:18][CH2:19][C:20](=[N:2][OH:3])[C:21]2[C:30]3[C:25](=[CH:26][CH:27]=[C:28]([O:31][CH3:32])[CH:29]=3)[N:24]=[CH:23][CH:22]=2)[C@@H:14]([C:34]([O:36][CH3:37])=[O:35])[CH2:13]1

Participants

5

Reactant 2

HCID 443297Hydroxyamine hydrochlorideHCID 53238403methyl (3R,4R)-1-[2-(thien-2-ylthio)ethyl]-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate

Product 1

HCID 136380445methyl (3R,4R)-1-[2-(thien-2-ylthio)ethyl]-4-[3-hydroxyimino-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylateYield 7.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1049PyridineSolvent

Conditions

Temperature
20 °C

Procedure

0.32 g of hydroxylamine hydrochloride is added, with stirring and under an inert atmosphere, to a mixture of 1.27 g of methyl (3R,4R)-1-[2-(thien-2-ylthio)ethyl]-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate in 13 cm3 of pyridine at a temperature in the region of 20° C. The mixture is stirred for 1 hour at a temperature in the region of 20° C. The resulting reaction mixture is diluted with 130 cm3 of distilled water and the mixture thus obtained is extracted with 50 cm3 of ethyl acetate and then two times with 30 cm3 of ethyl acetate. The combined organic phases are washed two times with 50 cm3 of distilled water, dried over magnesium sulfate and then concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue is purified by chromatography under a pressure of 50 kPa of nitrogen on a column of silica gel (particle size 20-45μ; weight of silica 160 g, diameter of the column 3.5 cm), elution being carried out with a mixture of ethyl acetate and cyclohexane (90/10 by volume). Fractions 20 to 22 are combined and then concentrated to dryness under the above conditions. 0.1 g of methyl (3R,4R)-1-[2-(thien-2-ylthio)ethyl]-4-[3-hydroxyimino-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate is obtained.

Workup

  1. customThe resulting reaction mixture
  2. customthe mixture thus obtained
  3. extractionis extracted with 50 cm3 of ethyl acetate
  4. washThe combined organic phases are washed two times with 50 cm3 of distilled water
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40° C
  7. customThe residue is purified by chromatography under a pressure of 50 kPa of nitrogen on a column of silica gel (particle size 20-45μ
  8. washweight of silica 160 g, diameter of the column 3.5 cm), elution
  9. additionbeing carried out with a mixture of ethyl acetate and cyclohexane (90/10 by volume)
  10. concentrationconcentrated to dryness under the above conditions

Sources & evidence

ORD record
ord-beb96a5e682a4648b8bf266d4b6c89b3
Source dataset
uspto-grants-2004_10
Patent number
US06806277B2

Reaction notes

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