Chloroacetone → 2-(2-Oxopropyl)cyclohexane-1,3-dione

HRID 1516977Notes

Reaction equation

HRID 1516977 reaction equation
[OH-].[K+].[C:3]1(=[O:10])[CH2:8][CH2:7][CH2:6][C:5](=[O:9])[CH2:4]1.Cl[CH2:12][C:13](=[O:15])[CH3:14]>O.CCO>[O:15]=[C:13]([CH3:14])[CH2:12][CH:4]1[C:5](=[O:9])[CH2:6][CH2:7][CH2:8][C:3]1=[O:10]

Participants

6

Reactant 3

HCID 6571ChloroacetoneHCID 104341,3-CyclohexanedioneHCID 14797Potassium Hydroxide

Product 1

HCID 44444072-(2-Oxopropyl)cyclohexane-1,3-dione

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A solution of KOH (2.54 kg, 2.26 kg corrected for assay, 40.2 moles) in water (4.0 L) was added over 30 mins to a solution of cyclohexane-1,3-dione (4.53 kg, 4.51 kg corrected for assay, 40.2 moles) in EtOH (16.2 L), while maintaining the temperature below 30° C. After stirring for 15 mins at r.t., freshly distilled chloroacetone (4.39 kg, 3.83 kg corrected for assay, 41.4 mol) was then added slowly to the mixture, maintaining a temperature of 25-28° C. The resulting slurry was stirred at r.t. for 19 h. Inorganic by-products were then removed by filtration and were washed on the filter with EtOH (4.5 L). The filtrates were combined to provide 2-(2-oxopropyl)cyclo-hexane-1,3-dione as a solution in EtOH. Assay by GC 26.5% w/w; purity by GC: 82.3 area %). This solution was transferred to a reactor and glycine ethyl ester hydrochloride salt (6.41 kg, 6.17 kg corrected for assay, 44.2 moles) was added at r.t. with stirring followed by sodium acetate trihydrate (6.04 kg, 6.02 kg corrected for assay, 44.3 moles). The mixture was diluted with ethanol (28.9 L) then heated under reflux for 2 h. EtOH was removed in vacuo (−0.850 to −0.900 bar) at 30° C. until 40 L of distillate had been collected. After cooling the residue to 0° C., water (15 L) was added, while maintaining a temperature of 0-5° C. After stirring for a further 1 h at this temperature, the solid that separated out was collected by filtration and was then dried in vacuo at 35° C. with a nitrogen bleed to give the title compound as a solid; 6.7 kg; assay by 1H NMR: 86.6% w/w; weight corrected for assay: 5.80 kg (61% over 2 steps); purity by GC: 96.0 area %; m/z: 235 (MH+); 1H NMR: (CDCl3) 1.27-1.32 (3H, t), 2.10-2.17 (2H, m), 2.19 (3H, s), 2.42-2.46 (2H, t), 2.65-2.69 (2H, t), 4.21-4.28 (2H, m), 4.51 (2H, s) and 6.27 (1H, s).

Workup

  1. temperaturewhile maintaining the temperature below 30° C
  2. temperaturemaintaining a temperature of 25-28° C
  3. stirringThe resulting slurry was stirred at r.t. for 19 h
  4. customInorganic by-products were then removed by filtration
  5. washwere washed on the
  6. filtrationfilter with EtOH (4.5 L)

Sources & evidence

ORD record
ord-5b58423b5d964b6cb4d43734998b098e
Source dataset
uspto-grants-2012_07
Patent number
US08227622B2

Reaction notes

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