Hydrochloric Acid → 2-(5,7-Difluoro-quinolin-6-yl)-malonic acid diethyl ester

HRID 655219Notes

Reaction equation

HRID 655219 reaction equation
[C:1]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:2][C:3]([O-:5])=[O:4].[H-].[Na+].Br[C:13]1[C:14]([F:24])=[C:15]2[C:20](=[CH:21][C:22]=1[F:23])[N:19]=[CH:18][CH:17]=[CH:16]2.Cl.O1CCO[CH2:28][CH2:27]1>O.COC(C)(C)C>[CH2:8]([O:7][C:1](=[O:6])[CH:2]([C:13]1[C:14]([F:24])=[C:15]2[C:20](=[CH:21][C:22]=1[F:23])[N:19]=[CH:18][CH:17]=[CH:16]2)[C:3]([O:5][CH2:27][CH3:28])=[O:4])[CH3:9]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 312751,4-DioxaneHCID 3595298Propanedioic acid, monoethyl esterHCID 451083546-Bromo-5,7-difluoroquinoline

Product 1

HCID 685295692-(5,7-Difluoro-quinolin-6-yl)-malonic acid diethyl esterYield 35.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

Ethyl malonate (9.28 g, 8.8 mL, 58.0 mmol) was added dropwise to a mixture of sodium hydride (60 percent in mineral oil, 2.32 g, 58.0 mmol) in 1,4-dioxane (29 mL) at 60° C. CuBr (4.176 g, 29.0 mmol) and 6-bromo-5,7-difluoro-quinoline (7.07 g, 29.0 mmol) were then added and the mixture heated to reflux for 16 h. After such time concentrated hydrochloric acid was added under ice-cooling and then tert-butyl methyl ether and water were added. The separated organic layer was washed with (10%) hydrochloric acid and water sequentially. Dried over sodium sulfate and concentrated. The residue was purified by column chromatography to afford the title compound (3.13 g, 35.4%).

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 16 h
  3. temperaturecooling
  4. washThe separated organic layer was washed with (10%) hydrochloric acid and water sequentially
  5. dry with materialDried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-139f0a285d1d4b75a767d828dfde68f2
Source dataset
uspto-grants-2011_12
Patent number
US08071581B2

Reaction notes

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