Diethyl Malonate → HCID 67099707, compound

HRID 2078268Notes

Reaction equation

HRID 2078268 reaction equation
[Cl:1][C:2]1[C:3]([F:14])=[C:4]([C:8]([CH3:13])([CH3:12])[C:9]([OH:11])=O)[CH:5]=[CH:6][CH:7]=1.S(Cl)(Cl)=O.[C:19]([O:27][CH2:28][CH3:29])(=[O:26])[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22].[Mg+2].[Cl-].[Cl-]>C(#N)C>[Cl:1][C:2]1[C:3]([F:14])=[C:4]([C:8]([CH3:13])([CH3:12])[C:9]([CH:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:19]([O:27][CH2:28][CH3:29])=[O:26])=[O:11])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 7761Diethyl MalonateHCID 24386Thionyl ChlorideHCID 5360315Magnesium ChlorideHCID 67099699HCID 67099699, compound

Product 1

HCID 67099707HCID 67099707, compoundYield 67.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
95 °C

Procedure

A mixture of 2-(3-chloro-2-fluorophenyl)-2-methylpropanoic acid (1.386 g, 6.40 mmol) and thionyl chloride (60.0 mL, 823 mmol) was stirred at 95° C. for 2 hours. The reaction was concentrated in vacuo, azeotroped using DCM (2×100 mL), and dried in vacuo to give the crude acid chloride. A solution of diethyl malonate (0.967 mL, 6.40 mmol) and MgCl2 (0.263 mL, 6.40 mmol) in ACN (40 mL) at 0° C., was treated dropwise with TEA (1.87 mL, 13.4 mmol), and the mixture was stirred at 25° C. for 3 hours. A solution of the acid chloride in ACN (35 mL) was added, and the mixture was stirred at 50° C. for 18 hours. The solution was concentrated in vacuo, diluted with 10% HCl(aq) (100 mL), and extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine (75 mL), dried over MgSO4, concentrated, and dried in vacuo. The residue was purified by flash column chromatography (silica, 0-100% DCM in hexane) to give 1.56 g of the title compound. MS m/e=325 (M+H)+.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customazeotroped
  3. customdried in vacuo
  4. customto give the crude acid chloride
  5. stirringthe mixture was stirred at 25° C. for 3 hours
  6. stirringthe mixture was stirred at 50° C. for 18 hours
  7. concentrationThe solution was concentrated in vacuo
  8. additiondiluted with 10% HCl(aq) (100 mL)
  9. extractionextracted with EtOAc (3×100 mL)
  10. washThe combined organic layers were washed with brine (75 mL)
  11. dry with materialdried over MgSO4
  12. concentrationconcentrated
  13. customdried in vacuo
  14. customThe residue was purified by flash column chromatography (silica, 0-100% DCM in hexane)

Sources & evidence

ORD record
ord-a924552b8d504f8289782ff23779f011
Source dataset
uspto-grants-2011_04
Patent number
US07928139B2

Reaction notes

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