Pyridine → HCID 54183868, compound

HRID 2081246Notes

Reaction equation

HRID 2081246 reaction equation
[Cl-].[Mg+2].[Cl-].[C:4]([O:10][CH3:11])(=[O:9])[CH2:5][C:6]([CH3:8])=[O:7].N1C=CC=CC=1.[Cl:18][C:19]1[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[C:20]=1[C:21](Cl)=[O:22].S(=O)(=O)(O)O.C(=O)([O-])[O-].[K+].[K+]>O.C1(C)C=CC=CC=1.C(#N)C>[Cl:18][C:19]1[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[C:20]=1[C:21]([CH2:8][C:6](=[O:7])[CH2:5][C:4]([O:10][CH3:11])=[O:9])=[O:22]

Participants

10

Reactant 6

HCID 1049PyridineHCID 1118Sulfuric AcidHCID 7757Methyl acetoacetateHCID 11430Potassium Carbonate2×HCID 783922,6-Dichlorobenzoyl chlorideHCID 5360315Magnesium Chloride

Product 1

HCID 54183868HCID 54183868, compoundYield 58.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

A slurry of anhydrous magnesium chloride (571 g, 6.0 moles) and methyl acetoacetate (697 g, 6.0 moles) in 3 1 of acetonitrile was stirred in an ice-salt bath as 972 ml of pyridine (12 moles) was added at such a rate that the temperature did not exceed 5° C. (addition time 2 hrs.). The cooling bath was removed and toluene (500 ml) was added at once followed by the addition of a solution of 1255 g of 2,6-dichlorobenzoyl chloride (6.0 moles) in 1.5 1 of toluene over one hour (final temperature 25° C.). The reaction was heated at reflux for 5 hours, and then allowed to cool over 14 hours to room temperature. The reaction was cooled in an ice bath to 0° C., and 400 ml of concentrated sulfuric acid (7.3 moles) was then added to the reaction mixture at a rate to maintain a temperature below 15° C., followed by 1.5 1 of water. The mixture was stirred for 30 min. The organic layer was isolated and washed with 3 1 of water. The acidic aqueous washes were back-extracted with 1 1 of toluene. The product was extracted from the combined organic layers with an aqueous potassium carbonate solution (3.6 moles in 3 1 water) and with a second potassium carbonate solution (0.4 moles in 1 1 water). The combined basic aqueous layers were washed with toluene (1 1) and acidified with concentrated hydrochloric acid. The resulting solid was isolated by filtration, washed with water (2×2 1), and dried under vacuum at 50° C. to give 1008 g (58%) of a granular orange solid.

Workup

  1. additionwas added at such a rate that the temperature
  2. customdid not exceed 5° C.
  3. addition(addition time 2 hrs.)
  4. customThe cooling bath was removed
  5. additiontoluene (500 ml) was added
  6. temperatureThe reaction was heated
  7. temperatureat reflux for 5 hours
  8. temperatureto cool over 14 hours to room temperature
  9. temperatureto maintain a temperature below 15° C.
  10. customThe organic layer was isolated
  11. washwashed with 3 1 of water
  12. extractionThe acidic aqueous washes were back-extracted with 1 1 of toluene
  13. washThe combined basic aqueous layers were washed with toluene (1 1)
  14. customThe resulting solid was isolated by filtration
  15. washwashed with water (2×2 1)
  16. customdried under vacuum at 50° C.

Sources & evidence

ORD record
ord-9551d1ee264b4cf6bc8c09de21fb2579
Source dataset
uspto-grants-1993_02
Patent number
US05183891

Reaction notes

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