Hydrochloric Acid → HCID 178424441, compound

HRID 1039579Notes

Reaction equation

HRID 1039579 reaction equation
[CH:1]1([C:4]2[CH:9]=[CH:8][CH:7]=[C:6]([CH3:10])[C:5]=2[OH:11])[CH2:3][CH2:2]1.CC(C)([O-])C.[Na+].[OH:18][C:19]1[CH:24]=[C:23]([Cl:25])[N:22]=[N:21][C:20]=1Cl.Cl>C1(C)C=CC=CC=1.O.C(O)(C)(C)C>[Cl:25][C:23]1[N:22]=[N:21][C:20]([O:11][C:5]2[C:6]([CH3:10])=[CH:7][CH:8]=[CH:9][C:4]=2[CH:1]2[CH2:3][CH2:2]2)=[C:19]([OH:18])[CH:24]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 229399512-Cyclopropyl-6-methylphenol2×HCID 23676156Sodium t-butoxideHCID 178516198HCID 178516198, compound

Product 1

HCID 178424441HCID 178424441, compoundYield 100.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 114.76 g (purity: 95.9%; 743 mmol) of 2-cyclopropyl-6-methylphenol and 70.0 g of t-butanol was charged into an autoclave, and 72.8 g (purity: 98.0%; 743 mmol) of sodium t-butoxide was added to the mixture over one hour, and then stirred at 70° C. for 30 minutes. The resultant solution was cooled to 40° C., and then 25.0 g (purity: 98%; 148.6 mmol) of 4-hydroxy-3,6-dichloropyridazine was added to the solution. Then, the resultant mixture was heated from 40° C. to 140° C. to effect a reaction for 24 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, and 750 g of pure water and 574 g of toluene were added to the cooled mixture and stirred for 30 minutes. Then, 41.7 g (400 mmol) of a 35% aqueous hydrochloric acid solution was added dropwise to the mixture, and an organic phase containing 2-cyclopropyl-6-methylphenol added in an excess amount was separated. 287 g of toluene was added to the resultant aqueous phase and stirred at room temperature for 30 minutes, and then an organic phase was separated. Then, the resultant aqueous phase containing a sodium salt of 6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol was added dropwise to 20.5 g (196 mmol) of a 35% aqueous hydrochloric acid solution at 0° C. to deposit solids, followed by filtration. The resultant solids were washed with pure water and dried under a reduced pressure, and dissolved in an organic solvent and quantitatively determined by an HPLC internal standard analysis method, which showed that 41.2 g of 6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol (purity: 85.4%; yield: 87.0%) and 29 mg of 3-chloro-6-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol (yield: 1.4%) were obtained.

Workup

  1. additionwas added to the mixture over one hour
  2. customa reaction for 24 hours
  3. customAfter completion of the reaction
  4. temperaturethe reaction mixture was cooled to room temperature
  5. stirringstirred for 30 minutes
  6. additionadded in an excess amount
  7. customwas separated
  8. addition287 g of toluene was added to the resultant aqueous phase
  9. stirringstirred at room temperature for 30 minutes
  10. customan organic phase was separated
  11. additionThen, the resultant aqueous phase containing a sodium salt of 6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinol
  12. additionwas added dropwise to 20.5 g (196 mmol) of a 35% aqueous hydrochloric acid solution at 0° C.
  13. filtrationfollowed by filtration
  14. washThe resultant solids were washed with pure water
  15. customdried under a reduced pressure
  16. dissolutiondissolved in an organic solvent

Sources & evidence

ORD record
ord-c274c217180148468bcb9d89197669cb
Source dataset
uspto-grants-2013_10
Patent number
US08552182B2

Reaction notes

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