Hydrochloric Acid → 3-(3-Fluoro-5-methyl-2-pyridyl)-4-chloro-5difluoromethoxy-1-methyl-[1H]-pyrazole

HRID 650489Notes

Reaction equation

HRID 650489 reaction equation
[F:1][C:2]1[C:3]([C:9]2[C:13]([Cl:14])=[C:12]([O:15][CH:16]([F:18])[F:17])[N:11]([CH3:19])[N:10]=2)=[N:4][CH:5]=[C:6](Cl)[CH:7]=1.Cl.O1CCOC[CH2:22]1>>[F:1][C:2]1[C:3]([C:9]2[C:13]([Cl:14])=[C:12]([O:15][CH:16]([F:18])[F:17])[N:11]([CH3:19])[N:10]=2)=[N:4][CH:5]=[C:6]([CH3:22])[CH:7]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 217121353-(3-fluoro-5-chloro-2-pyridyl)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole

Product 1

HCID 217121433-(3-Fluoro-5-methyl-2-pyridyl)-4-chloro-5difluoromethoxy-1-methyl-[1H]-pyrazole

Conditions

Temperature
90 °C

Procedure

2.0 g of 3-(3-fluoro-5-chloro-2-pyridyl)-4-chloro-5-difluoromethoxy-1-methyl-[1H]-pyrazole (Example P15) are introduced into 6 ml of absolute dioxane. In order to remove the oxygen, gentle evacuation is carried out three times (water-jet pump) and the mixture is gassed with argon. 6.4 ml of a 2M solution of trimethylaiuminium in toluene and 0.10 g of tetrakistriphenylphosphinepalladium (Pd(PPh3)4) are added thereto. The mixture is heated to 90° C., with stirring, in an argon atmosphere. The next day the mixture is cooled to 22° C., a further 0.10 g of Pd(PPh3)4 and 6.4 ml of a 2M solution of trimethylaluminium in toluene are added and the mixture is stirred at 110° C. After 4 hours, TLC analysis of a worked-up sample shows that all the starting material has reacted. The reaction mixture is introduced carefully into cold, dilute hydrochloric acid and is then extracted with ethyl acetate. The combined organic phases are washed with brine, dried over sodium sulfate, filtered and concentrated by evaporation in vacuo. The crude product obtained is purified over a flash chromatography column (silica gel; eluant: n-hexane/ethyl acetate 1/1 (v/v)). 1.36 g of the desired compound are obtained in the form of a yellow oil, which slowly crystallises; melting point 41-42° C.

Workup

  1. customIn order to remove the oxygen, gentle evacuation
  2. addition6.4 ml of a 2M solution of trimethylaiuminium in toluene and 0.10 g of tetrakistriphenylphosphinepalladium (Pd(PPh3)4) are added
  3. temperatureThe next day the mixture is cooled to 22° C.
  4. additiona further 0.10 g of Pd(PPh3)4 and 6.4 ml of a 2M solution of trimethylaluminium in toluene are added
  5. stirringthe mixture is stirred at 110° C
  6. customTLC analysis of a worked-up sample shows that all the starting material has reacted
  7. extractionis then extracted with ethyl acetate
  8. washThe combined organic phases are washed with brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated by evaporation in vacuo
  12. customThe crude product obtained
  13. customis purified over a flash chromatography column (silica gel; eluant: n-hexane/ethyl acetate 1/1 (v/v))

Sources & evidence

ORD record
ord-87443606ef674155b699556c6bb92df1
Source dataset
uspto-grants-2001_08
Patent number
US06274536B1

Reaction notes

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