Diethyl Malonate → HCID 13646818, compound

HRID 364802Notes

Reaction equation

HRID 364802 reaction equation
[C:1]([O:9]CC)(=[O:8])[CH2:2][C:3](OCC)=O.[H-].[Na+].FC(F)(F)S(OC1[CH:21]=[C:22]2[C:26](=[C:27]([Cl:30])[C:28]=1[Cl:29])[C:25](=[O:31])[C:24]([CH2:33][CH:34]1[CH2:38][CH2:37][CH2:36][CH2:35]1)([CH3:32])[CH2:23]2)(=O)=O>CN(C)C=O.C1(C)C=CC=CC=1>[Cl:29][C:28]1[C:27]([Cl:30])=[C:26]2[C:22]([CH2:23][C:24]([CH2:33][CH:34]3[CH2:35][CH2:36][CH2:37][CH2:38]3)([CH3:32])[C:25]2=[O:31])=[CH:21][C:3]=1[CH2:2][C:1]([OH:9])=[O:8]

Participants

6

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 20193577HCID 20193577, compound

Product 1

HCID 13646818HCID 13646818, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

Diethyl malonate (18.3 g., 0.114 mole) is added with stirring under nitrogen at 10°-15° C. to a suspension of sodium hydride (56% in mineral oil, 4.89 g., 0.114 mole) in dry dimethylformamide (85 ml.). The reaction mixture is stirred for 1 hour at room temperature, cooled to 5° C. and then 6,7-dichloro-2-cyclopentylmethyl-2,3-dihydro-2-methyl-1-oxo-1H-inden-5-yl trifluoromethanesulfonate (18.8 g., 0.0426 mole dissolved in dry toluene (20 ml.) is added over 1 hour at 5°-7° C. After stirring at room temperature for 18 hours, the reaction mixture is poured into ice water (1000 ml.) and extracted with ether (4×150 ml.) and the with methylene chloride (2×50 ml.). The combined organic extracts are washed three times with water and concentrated under vacuum. The residual oil is dissolved in ethanol (150 ml.) and added to a solution of 20 g. of sodium hydroxide in water (150 ml.). The mixture is refluxed for 3 hours, cooled and the ethanol removed under vacuum. The residue is diluted with water, extracted with hexane and then acidified with hydrochloric acid. The gum that separates is extracted with ether. The combined etheral extracts are washed with water and then extracted repeatedly with dilute sodium bicarbonate. The combined aqueous extracts are acidified with hydrochloric acid and extracted with ether. The ether extracts are washed with brine, dried over magnesium sulfate an concentrated under vacuum to obtain the crude (6,7-dichloro-2-cyclopentylmethyl-2,3-dihydro-2-methyl-1-oxo-1H-inden-5-yl)acetic acid, 9.3 g., m.p. 145.5°-148° C., in 62% yield. Recrystallization from butyl chloride affords material which melts at 149°-151° C.

Workup

  1. temperaturecooled to 5° C.
  2. additionis added over 1 hour at 5°-7° C
  3. stirringAfter stirring at room temperature for 18 hours
  4. extractionextracted with ether (4×150 ml.)
  5. washThe combined organic extracts are washed three times with water
  6. concentrationconcentrated under vacuum
  7. dissolutionThe residual oil is dissolved in ethanol (150 ml.)
  8. additionadded to a solution of 20 g
  9. temperatureThe mixture is refluxed for 3 hours
  10. temperaturecooled
  11. customthe ethanol removed under vacuum
  12. additionThe residue is diluted with water
  13. extractionextracted with hexane
  14. extractionThe gum that separates is extracted with ether
  15. washThe combined etheral extracts are washed with water
  16. extractionextracted repeatedly with dilute sodium bicarbonate
  17. extractionextracted with ether
  18. washThe ether extracts are washed with brine
  19. dry with materialdried over magnesium sulfate
  20. concentrationan concentrated under vacuum

Sources & evidence

ORD record
ord-737ace52b9614356860ed753b478c4c6
Source dataset
uspto-grants-1986_08
Patent number
US04605663

Reaction notes

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