Diethyl Malonate → HCID 67099240, compound

HRID 2078105Notes

Reaction equation

HRID 2078105 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]([CH3:13])([CH3:12])[C:9]([OH:11])=O.C(Cl)(=O)C(Cl)=O.[C:20]([O:28][CH2:29][CH3:30])(=[O:27])[CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23].[Mg+2].[Cl-].[Cl-]>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]([CH3:13])([CH3:12])[C:9]([CH:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:20]([O:28][CH2:29][CH3:30])=[O:27])=[O:11]

Participants

6

Reactant 4

HCID 7761Diethyl MalonateHCID 65578Oxalyl chlorideHCID 5360315Magnesium ChlorideHCID 259167252-(2-Fluorophenyl)-2-methylpropanoic acid

Product 1

HCID 67099240HCID 67099240, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(2-fluorophenyl)-2-methylpropanoic acid (3.98 g, 22 mmol), IPAc (31 mL) and DMF (0.017 mL), was slowly added oxalyl chloride (2.0 mL, 23 mmol) over 10 minutes. The resulting solution was stirred for 16 hours and then concentrated in vacuo to afford an oil. In a separate flask, IPAc (30.0 mL) and diethyl malonate (4.2 mL, 27 mmol) were combined. To this mixture was added anhydrous MgCl2 (2.6 g, 27 mmol). The resulting white slurry was stirred at room temperature for 30 minutes, and then TEA (10 mL, 73 mmol) was added. After stirring for an additional 2.5 hours, the reaction was chilled in an ice water bath for 10 minutes, and then the crude acid chloride (previously prepared above) was added to the white mixture via syringe over 10 minutes. The ice bath was removed, and the reaction was stirred for 1.5 hours at room temperature. The mixture was acidified with 5N HCl and added IPAc (50 mL) was added. The aqueous layer was separated and set aside. The organic layer was sequentially washed with saturated NaHCO3 solution and then water. The separated organic layer was dried over Na2SO4, filtered, and concentrated in vacuo to give the crude product. MS (m/z)=325 (M+H)+.

Workup

  1. customover 10 minutes
  2. concentrationconcentrated in vacuo
  3. customto afford an oil
  4. stirringThe resulting white slurry was stirred at room temperature for 30 minutes
  5. stirringAfter stirring for an additional 2.5 hours
  6. temperaturethe reaction was chilled in an ice water bath for 10 minutes
  7. additionwas added to the white mixture via syringe over 10 minutes
  8. customThe ice bath was removed
  9. stirringthe reaction was stirred for 1.5 hours at room temperature
  10. additionadded IPAc (50 mL)
  11. additionwas added
  12. customThe aqueous layer was separated
  13. washThe organic layer was sequentially washed with saturated NaHCO3 solution
  14. dry with materialThe separated organic layer was dried over Na2SO4
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-533217fc4780484595c0dd0a912646bb
Source dataset
uspto-grants-2011_04
Patent number
US07928139B2

Reaction notes

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