Sodium Hydroxide → HCID 69353164, compound

HRID 2186361Notes

Reaction equation

HRID 2186361 reaction equation
[OH:1][CH:2]([C:22]1[C:31]2[C:26](=[CH:27][CH:28]=[C:29]([O:32][CH3:33])[CH:30]=2)[N:25]=[CH:24][CH:23]=1)[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]#[C:13][C:14]2[CH:18]=[CH:17][S:16][CH:15]=2)[CH2:7][C@@H:6]1[C:19]([O-:21])=[O:20].[OH-].[Na+]>O1CCOCC1>[OH:1][CH:2]([C:22]1[C:31]2[C:26](=[CH:27][CH:28]=[C:29]([O:32][CH3:33])[CH:30]=2)[N:25]=[CH:24][CH:23]=1)[CH2:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][N:8]([CH2:11][C:12]#[C:13][C:14]2[CH:18]=[CH:17][S:16][CH:15]=2)[CH2:7][C@@H:6]1[C:19]([OH:21])=[O:20]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 131723274HCID 131723274, compound

Product 1

HCID 69353164HCID 69353164, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
20 °C

Procedure

A solution of 0.73 g of methyl. (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(thien-3-yl)prop-2-ynyl]piperidine-3-carboxylate, 7.6 cm3 of dioxane, and 1.22 cm3 of 5N aqueous sodium hydroxide solution was heated at a temperature in the region of 60° C. with stirring for 3 hours 30 minutes. After cooling to a temperature in the region of 20° C., the reaction mixture was concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained was purified by chromatography under argon pressure (55 kPa) on a column of silica gel (particle size 40-63 μm; diameter 5 cm; silica volume 120 cm3), elution was carried out first with 1120 cm3 of a dichloromethane/methanol/acetonitrile (92/8/7 by volume) mixture. Elution was subsequently carried out with 224 cm3 of the same mixture (but with a composition of 92/12/7 by volume), then 224 cm3 of the same mixture (with a composition of 92/16/7 by volume), then 400 cm3 of a dichloromethanel methanol (50/50 by volume) mixture, and finally 400 cm3 of pure methanol. A fraction of 112 cm3 was collected, followed by 7-cm3 fractions. Fractions 173 to 468 were combined and then evaporated under reduced pressure (2 kPa) at a temperature in the region of 35° C. A foam was obtained, which foam was dried under reduced pressure (30 Pa) at a temperature in the region of 30° C. for 4 to 5 hours. 0.33 g of (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(thien-3-yl)prop-2-ynyl]piperidine-3-carboxylic acid was obtained in the form of a beige-colored solid with a foamy appearance melting at 113-115° C.

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  2. customThe residue obtained
  3. customwas purified by chromatography under argon pressure (55 kPa)
  4. washon a column of silica gel (particle size 40-63 μm; diameter 5 cm; silica volume 120 cm3), elution
  5. washElution
  6. customA fraction of 112 cm3 was collected
  7. customevaporated under reduced pressure (2 kPa) at a temperature in the region of 35° C
  8. customA foam was obtained
  9. customwhich foam was dried under reduced pressure (30 Pa) at a temperature in the region of 30° C. for 4 to 5 hours

Sources & evidence

ORD record
ord-ac04d3d0d51a44fdac5bad6c8d4f9e81
Source dataset
uspto-grants-2002_06
Patent number
US06403610B1

Reaction notes

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