Water → methyl (3R,4R)-1-(3-prop-2-ynyl)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate

HRID 393219Notes

Reaction equation

HRID 393219 reaction equation
C(N(CC)CC)C.[CH2:8](Br)[C:9]#[CH:10].[O:12]=[C:13]([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)[CH2:14][CH2:15][C@@H:16]1[CH2:21][CH2:20][NH:19][CH2:18][C@@H:17]1[C:22]([O:24][CH3:25])=[O:23].O>CN(C)C=O.C(OCC)(=O)C>[CH3:8][C:9]#[C:10][N:19]1[CH2:20][CH2:21][C@@H:16]([CH2:15][CH2:14][C:13](=[O:12])[C:26]2[C:35]3[C:30](=[CH:31][CH:32]=[C:33]([O:36][CH3:37])[CH:34]=3)[N:29]=[CH:28][CH:27]=2)[C@@H:17]([C:22]([O:24][CH3:25])=[O:23])[CH2:18]1

Participants

7

Reactant 4

HCID 962WaterHCID 7842Propargyl bromideHCID 8471TriethylamineHCID 53238173(3R,4R)-methyl 4-(3-(6-methoxyquinolin-4-yl)-3-oxopropyl)piperidine-3-carboxylate

Product 1

HCID 86591491methyl (3R,4R)-1-(3-prop-2-ynyl)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

23.7 cm3 of triethylamine and 6.35 cm3 of propargyl bromide are added at a temperature in the region of 20° C., with stirring and under an inert atmosphere, to a solution of 14.43 g of methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate in 350 cm3 of anhydrous dimethylformamide. After heating for 5 hours at a temperature in the region of 45° C., the reaction mixture is cooled to approximately 20° C., poured into 190 cm3 of water and 190 cm3 of ethyl acetate, and then extracted with 3 times 250 cm3 of ethyl acetate. The organic extracts are combined, washed 3 times with 250 cm3 of water, dried over sodium sulfate, filtered and concentrated under reduced pressure (1 kPa) at a temperature in the region of 50° C. The residue is purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45μ; diameter 8 cm; mass 600 g), elution being carried out with ethyl acetate and an ethyl acetate/methanol (95/05 by volume) mixture and 400-cm3 fractions being collected. Fractions 3 to 13 are combined and then concentrated under the above conditions. 17.5 g of methyl (3R,4R)-1-(3-prop-2-ynyl)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate are obtained.

Workup

  1. temperaturethe reaction mixture is cooled to approximately 20° C.
  2. extractionextracted with 3 times 250 cm3 of ethyl acetate
  3. washwashed 3 times with 250 cm3 of water
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure (1 kPa) at a temperature in the region of 50° C
  7. customThe residue is purified by chromatography at atmospheric pressure on a column of silica gel (particle size 20-45μ; diameter 8 cm; mass 600 g), elution
  8. customan ethyl acetate/methanol (95/05 by volume) mixture and 400-cm3 fractions being collected
  9. concentrationconcentrated under the above conditions

Sources & evidence

ORD record
ord-474950c3c6b042a794d9198235acce32
Source dataset
uspto-grants-2004_10
Patent number
US06806277B2

Reaction notes

Loading…