Acetic Acid → 2-(2-Fluoro-4-chloro-5-isopropoxyphenyl)-4-methyl-5-trifluoromethylpyridazin-3-one

HRID 2271237Notes

Reaction equation

HRID 2271237 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH:9]([CH3:11])[CH3:10])=[CH:6][C:5]([NH:12][N:13]=[CH:14][C:15](=O)[C:16]([F:19])([F:18])[F:17])=[C:4]([F:21])[CH:3]=1.N1CCCCC1.[CH3:28][CH:29](C(O)=O)[C:30](O)=[O:31].C(O)(=O)C>N1C=CC=CC=1>[F:21][C:4]1[CH:3]=[C:2]([Cl:1])[C:7]([O:8][CH:9]([CH3:11])[CH3:10])=[CH:6][C:5]=1[N:12]1[C:30](=[O:31])[C:29]([CH3:28])=[C:15]([C:16]([F:19])([F:18])[F:17])[CH:14]=[N:13]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 487Methylmalonic AcidHCID 8082PiperidineHCID 691414303,3,3-Trifluoro-2-oxopropanal 1-(4-chloro-2-fluoro-5-isopropoxyphenylhydrazone)

Product 1

HCID 110898282-(2-Fluoro-4-chloro-5-isopropoxyphenyl)-4-methyl-5-trifluoromethylpyridazin-3-oneYield 57.2%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
70 °C

Procedure

Under a stream of nitrogen gas, 0.399 g of 3,3,3-trifluoro-2-oxopropanal 1-(4-chloro-2-fluoro-5-isopropoxyphenylhydrazone), compound 3-3 was dissolved in 2.4 ml of pyridine at room temperature. To this solution were added 0.133 ml of piperidine and 0.159 g of methylmalonic acid, and the mixture was heated to 70° C. and stirred for 3.5 hours. Then, 2.4 ml of acetic acid was added, and stirring was further continued at 130° C. for 8 hours. The reaction solution was left cooling to room temperature and concentrated under reduced pressure. The residue was diluted with 100 ml of diethyl ether. The diluted solution was washed twice with 20 ml of 3 N hydrochloric acid and once with 30 m of saturated sodium bicarbonate solution, dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was subjected to column chromatography to give 0.255 g of 2-(2-fluoro-4-chloro-5-isopropoxyphenyl)-4-methyl-5-trifluoromethylpyridazin-3-one, compound 5-2.

Workup

  1. stirringstirring
  2. waitwas further continued at 130° C. for 8 hours
  3. waitThe reaction solution was left
  4. temperaturecooling to room temperature
  5. concentrationconcentrated under reduced pressure
  6. additionThe residue was diluted with 100 ml of diethyl ether
  7. washThe diluted solution was washed twice with 20 ml of 3 N hydrochloric acid and once with 30 m of saturated sodium bicarbonate solution
  8. dry with materialdried with magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-fbfcb9d2fe7d4284a2a4eff2403b6e56
Source dataset
uspto-grants-2001_12
Patent number
US06333413B1

Reaction notes

Loading…