Diethyl Malonate → 5-(5-Fluoro-2-methylphenyl)cyclohexane-1,3-dione

HRID 49190Notes

Reaction equation

HRID 49190 reaction equation
[O-:1][CH2:2][CH3:3].[Na+].C(OCC)(=O)CC(OCC)=O.[F:16][C:17]1[CH:18]=[CH:19][C:20]([CH3:28])=[C:21]([CH:23]=[CH:24][C:25](=[O:27])[CH3:26])[CH:22]=1>C(O)C>[F:16][C:17]1[CH:18]=[CH:19][C:20]([CH3:28])=[C:21]([CH:23]2[CH2:3][C:2](=[O:1])[CH2:26][C:25](=[O:27])[CH2:24]2)[CH:22]=1

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 2723922Sodium ethoxideHCID 540396424-(5-Fluoro-2-methylphenyl)-3-buten-2-one

Product 1

HCID 183177715-(5-Fluoro-2-methylphenyl)cyclohexane-1,3-dione

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A 20% solution of sodium ethoxide in ethanol (29.7 g) was combined at 0C with diethyl malonate (14.0 g) and then with 4-(5-fluoro-2-methylphenyl)-3-buten-2-one (13.4 g) in portions. The reaction mixture was stirred at room temperature for 30 minutes, and then stirred with heating for 2 hours. After allowing to stand to cool, the solvent was distilled off, and the residue was combined with water and the aqueous layer was washed with ethyl acetate and then concentrated. 2M Sodium hydroxide (46 ml) was added and the mixture was heated under reflux for 1 hour. After allowing to stand to cool, 2.5M sulfuric acid (46 ml) was added over 10 minutes, and the mixture was heated under reflux for 30 minutes. After allowing to stand to cool, the precipitated crystal was recovered by a filtration and washed successively with water and isopropyl ether to obtain 5-(5-fluoro-2-methylphenyl)cyclohexane-1,3-dione (8.6 g) as a colorless crystal.

Workup

  1. stirringstirred
  2. temperaturewith heating for 2 hours
  3. temperatureto cool
  4. distillationthe solvent was distilled off
  5. washthe aqueous layer was washed with ethyl acetate
  6. concentrationconcentrated
  7. addition2M Sodium hydroxide (46 ml) was added
  8. temperaturethe mixture was heated
  9. temperatureunder reflux for 1 hour
  10. temperatureto cool
  11. addition2.5M sulfuric acid (46 ml) was added over 10 minutes
  12. temperaturethe mixture was heated
  13. temperatureunder reflux for 30 minutes
  14. temperatureto cool
  15. filtrationthe precipitated crystal was recovered by a filtration
  16. washwashed successively with water and isopropyl ether

Sources & evidence

ORD record
ord-6e571047d1ce479ebee81a8e47032fe3
Source dataset
uspto-grants-2004_03
Patent number
US06706732B1

Reaction notes

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