Diethyl Malonate → HCID 67099760, compound

HRID 1868637Notes

Reaction equation

HRID 1868637 reaction equation
[CH3:1][C:2]([C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=1)([CH3:6])[C:3]([OH:5])=O.S(Cl)(Cl)=O.[Mg].[C:22]([O:30][CH2:31][CH3:32])(=[O:29])[CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25]>C1COCC1.C(OCC)C.C(Cl)(Cl)(Cl)Cl.CCO>[CH3:6][C:2]([C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=1)([CH3:1])[C:3]([CH:23]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:22]([O:30][CH2:31][CH3:32])=[O:29])=[O:5]

Participants

9

Reactant 4

HCID 7761Diethyl MalonateHCID 24386Thionyl ChlorideHCID 5462224MagnesiumHCID 217064942-Methyl-2-[4-(trifluoromethyl)phenyl]propanoic acid

Product 1

HCID 67099760HCID 67099760, compoundYield 52.2%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 3283Diethyl EtherSolventHCID 5943Carbon TetrachlorideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
23 °C

Procedure

A solution of 2-methyl-2-(4-(trifluoromethyl)phenyl)propanoic acid (1325 mg, 5706 μmol) in thionyl chloride (4162 μL, 57063 μmol) was heated at reflux under nitrogen. After 2 hours, the reaction was cooled to 23° C. and concentrated in vacuo to afford the crude acid chloride. In an oven-dried round-bottomed flask, magnesium (208 mg, 8559 μmol) and diethyl malonate (1293 μL, 8559 μmol) were added to EtOH (15 mL) and CCl4 (0.2 mL). The reaction was stirred at 23° C. for 30 minutes followed by the addition of THF (15 mL). The reaction was heated to reflux under nitrogen. After 1 hour, a solution of the crude acid chloride in THF (10 mL) was added in a drop wise fashion. After 30 minutes, the reaction was cooled to 23° C., diluted with diethyl ether (150 mL), and washed with water (150 mL). The aqueous layer was extracted with diethyl ether (150 mL). The combined ether layers were washed with brine (100 mL), dried over MgSO4, concentrated in vacuo, and purified on silica gel (eluant: 5-20% EtOAc/hexane) affording 1115 mg of the title compound. MS m/e=375.2 (M+H)+.

Workup

  1. temperatureat reflux under nitrogen
  2. concentrationconcentrated in vacuo
  3. customto afford the crude acid chloride
  4. temperatureThe reaction was heated
  5. temperatureto reflux under nitrogen
  6. waitAfter 1 hour
  7. waitAfter 30 minutes
  8. temperaturethe reaction was cooled to 23° C.
  9. washwashed with water (150 mL)
  10. extractionThe aqueous layer was extracted with diethyl ether (150 mL)
  11. washThe combined ether layers were washed with brine (100 mL)
  12. dry with materialdried over MgSO4
  13. concentrationconcentrated in vacuo
  14. custompurified on silica gel (eluant: 5-20% EtOAc/hexane)

Sources & evidence

ORD record
ord-5d778e7af4df43d6bec9f2f7105a80d7
Source dataset
uspto-grants-2009_12
Patent number
US07635715B2

Reaction notes

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