Diethyl Malonate → HCID 67099936, compound

HRID 1868841Notes

Reaction equation

HRID 1868841 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1([C:14]([OH:16])=O)[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1.C(Cl)(=O)C(Cl)=O.[C:23]([O:31][CH2:32][CH3:33])(=[O:30])[CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26].[Mg+2].[Cl-].[Cl-]>C(Cl)Cl.CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1([C:14]([CH:24]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[C:23]([O:31][CH2:32][CH3:33])=[O:30])=[O:16])[CH2:9][CH2:10][O:11][CH2:12][CH2:13]1

Participants

7

Reactant 4

HCID 7761Diethyl MalonateHCID 65578Oxalyl chlorideHCID 5360315Magnesium ChlorideHCID 176091224-(2-Fluorophenyl)oxane-4-carboxylic acid

Product 1

HCID 67099936HCID 67099936, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 4-(2-fluorophenyl)-tetrahydro-2H-pyran-4-carboxylic acid (1.9 g, 8.5 mmol) in DCM (50 mL) and DMF (5 mL) was carefully added oxalyl chloride (0.79 mL, 8.9 mmol). Gas evolution was observed. The reaction was stirred at room temperature for 3 hours. In a separate flask was combined IPAc (1.0 mL, 8.7 mmol), diethyl malonate (1.6 mL, 11 mmol). and anhydrous MgCl2 (1.0 g, 11 mmol). The resulting white slurry was stirred for 30 minutes, and then TEA (4.0 mL, 29 mmol) was added and the reaction was stirred for 2.5 hours. The reaction was chilled in an ice water bath for 10 minutes, and then the concentrated acid chloride oil was added via syringe over 10 minutes. The ice bath was removed, and the reaction was stirred for 16 hours at 50° C. After cooling to room temperature, the reaction was acidified with 5N HCl solution (100 mL). The aqueous layer was removed, and the organic layer was washed with saturated NaHCO3 solution (150 mL). The aqueous layer was removed, and the organic extract was washed with water. The organic layer was dried (Na2SO4), filtered and concentrated to afford a dark colored oil. The crude reaction mixture was used in the next step.

Workup

  1. customIn a separate flask was combined
  2. stirringThe resulting white slurry was stirred for 30 minutes
  3. stirringthe reaction was stirred for 2.5 hours
  4. temperatureThe reaction was chilled in an ice water bath for 10 minutes
  5. customThe ice bath was removed
  6. stirringthe reaction was stirred for 16 hours at 50° C
  7. temperatureAfter cooling to room temperature
  8. customThe aqueous layer was removed
  9. washthe organic layer was washed with saturated NaHCO3 solution (150 mL)
  10. customThe aqueous layer was removed
  11. extractionthe organic extract
  12. washwas washed with water
  13. dry with materialThe organic layer was dried (Na2SO4)
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customto afford a dark colored oil
  17. customThe crude reaction mixture

Sources & evidence

ORD record
ord-1d1f6d4e6baf4d57b1e06678d513a554
Source dataset
uspto-grants-2009_12
Patent number
US07635715B2

Reaction notes

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