Hydroxyamine hydrochloride → methyl (3R,4R)-1-[3-(2,3,5-trifluorophenyl)prop-2-ynyl]-4-[3-hydroxyimino-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate

HRID 393217Notes

Reaction equation

HRID 393217 reaction equation
Cl.[NH2:2][OH:3].[F:4][C:5]1[C:10]([F:11])=[CH:9][C:8]([F:12])=[CH:7][C:6]=1[C:13]#[C:14][CH2:15][N:16]1[CH2:21][CH2:20][C@@H:19]([CH2:22][CH2:23][C:24](=O)[C:25]2[C:34]3[C:29](=[CH:30][CH:31]=[C:32]([O:35][CH3:36])[CH:33]=3)[N:28]=[CH:27][CH:26]=2)[C@@H:18]([C:38]([O:40][CH3:41])=[O:39])[CH2:17]1>N1C=CC=CC=1>[F:4][C:5]1[C:10]([F:11])=[CH:9][C:8]([F:12])=[CH:7][C:6]=1[C:13]#[C:14][CH2:15][N:16]1[CH2:21][CH2:20][C@@H:19]([CH2:22][CH2:23][C:24](=[N:2][OH:3])[C:25]2[C:34]3[C:29](=[CH:30][CH:31]=[C:32]([O:35][CH3:36])[CH:33]=3)[N:28]=[CH:27][CH:26]=2)[C@@H:18]([C:38]([O:40][CH3:41])=[O:39])[CH2:17]1

Participants

4

Reactant 2

HCID 443297Hydroxyamine hydrochlorideHCID 86591490(3R,4R)-methyl 4-(3-(6-methoxyquinolin-4-yl)-3-oxopropyl)-1-(3-(2,3,5-trifluorophenyl)prop-2-ynyl)piperidine-3-carboxylate

Product 1

HCID 136380444methyl (3R,4R)-1-[3-(2,3,5-trifluorophenyl)prop-2-ynyl]-4-[3-hydroxyimino-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylateYield 93.1%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
20 °C

Procedure

0.834 g of hydroxylamine hydrochloride is added, with stirring and under an inert atmosphere, to a mixture of 3.5 g of methyl (3R,4R)-1-[3-(2,3,5-trifluorophenyl)prop-2-ynyl]-4-[3oxo-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate in 35 cm3 of pyridine at a temperature in the region of 20° C. The mixture is stirred for 5 hours at a temperature in the region of 20° C. The reaction mixture is concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue is taken up in 300 cm3 of ethyl acetate and 100 cm3 of water. After standing for 16 hours, the mixture is extracted with 3 times 100 cm3 of ethyl acetate. The organic extracts are combined, washed with 3 times 100 cm3 of water, dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40° C. 3.35 g of methyl (3R,4R)-1-[3-(2,3,5-trifluorophenyl)prop-2-ynyl]-4-[3-hydroxyimino-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate are obtained.

Workup

  1. concentrationThe reaction mixture is concentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40° C
  2. waitAfter standing for 16 hours
  3. extractionthe mixture is extracted with 3 times 100 cm3 of ethyl acetate
  4. washwashed with 3 times 100 cm3 of water
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure (5 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-0d9960bb715d4d6e998d2b83f0d2799e
Source dataset
uspto-grants-2004_10
Patent number
US06806277B2

Reaction notes

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