Hydrochloric Acid → Diethyl 2-(3-(trifluoromethyl)pyridin-2-yl)malonate

HRID 1907677

Reaction equation

HRID 1907677 reaction equation
[H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].Cl[C:15]1[C:20]([C:21]([F:24])([F:23])[F:22])=[CH:19][CH:18]=[CH:17][N:16]=1.Cl>O1CCOCC1.[Cu](Cl)Cl.C(OCC)(=O)C.O>[F:22][C:21]([F:24])([F:23])[C:20]1[C:15]([CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:3]([O:11][CH2:12][CH3:13])=[O:10])=[N:16][CH:17]=[CH:18][CH:19]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 5898332-Chloro-3-(trifluoromethyl)pyridine

Product 1

HCID 57950213Diethyl 2-(3-(trifluoromethyl)pyridin-2-yl)malonateYield 27.4%

Reagents, catalysts & solvents 4

HCID 24014Cupric ChlorideCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×

Procedure

8.73 g of sodium hydride (55% oil dispersion) was suspended in 100 ml of 1,4-dioxane. Into this, 32.03 g of diethyl malonate was added dropwise over a period of about 1 hour at 60° C. under a nitrogen atmosphere. The mixture was stirred further for 0.5 hours at the same temperature, then, 8.26 g of copper chloride (I) was added to the mixture. Thereafter, into the mixture, a solution prepared by dissolving 15.00 g of 2-chloro-3-(trifluoromethyl)pyridine in 50 ml of 1,4-dioxane at 80° C. was dropped. The mixture was stirred for 16 hours under reflux with heating. The reaction mixture was allowed to cool to room temperature, and to the reaction mixture was added 15 ml of concentrated hydrochloric acid. To the mixture were added water and ethyl acetate, and the mixture was filtrated through celite. The filtrate was liquid-separated. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. 51.14 g of the resultant residue was subjected to silica gel column chromatography, to obtain 6.90 g of diethyl (3-trifluoromethyl-2-pyridyl)malonate.

Workup

  1. customThereafter, into the mixture, a solution prepared
  2. additionwas dropped
  3. stirringThe mixture was stirred for 16 hours
  4. temperatureunder reflux
  5. temperaturewith heating
  6. filtrationthe mixture was filtrated through celite
  7. customThe filtrate was liquid-separated
  8. washThe organic layer was washed with saturated brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c664465c17ad4d7dbb08de2c0cb69feb
Source dataset
uspto-grants-2013_12
Patent number
US08598176B2

Linked notes

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