Ethanol → 3-(3-Fluoro-5-chloro-2-pyridyl)-5-ethoxycarbonyl-1-methyl-[1H]-pyrazole

HRID 650486Notes

Reaction equation

HRID 650486 reaction equation
[F:1][C:2]1[C:3]([C:9]2[CH:13]=[C:12](Br)[N:11]([CH3:15])[N:10]=2)=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.C(N([CH2:21][CH3:22])CC)C.[C]=[O:24].[CH2:25]([OH:27])C>>[CH2:21]([O:24][C:25]([C:12]1[N:11]([CH3:15])[N:10]=[C:9]([C:3]2[C:2]([F:1])=[CH:7][C:6]([Cl:8])=[CH:5][N:4]=2)[CH:13]=1)=[O:27])[CH3:22]

Participants

5

Reactant 4

HCID 702EthanolHCID 8471TriethylamineHCID 217121223-(3-Fluoro-5-chloro-2-pyridyl)-5-bromo-1-methyl-[1H]-pyrazoleHCID 178418416HCID 178418416, compound

Product 1

HCID 220135663-(3-Fluoro-5-chloro-2-pyridyl)-5-ethoxycarbonyl-1-methyl-[1H]-pyrazole

Conditions

Temperature
100 °C

Procedure

5.0 g of 3-(3-fluoro-5-chloro-2-pyridyl)-5-bromo-1-methyl-[1H]-pyrazole (Example P18) are introduced into an autoclave together with 7.2 ml of triethylamine, 0.48 g of bis-triphenylphosphinepalladium dichloride (PdCl2(PPh3)2) and 70 ml of absolute ethanol. At 22° C. a pressure of 100 bar is applied with carbon monoxide and the reaction mixture is maintained at 100° C. for 48 hours. In the meantime a further 0.48 g of bis-triphenylphosphinepalladium dichloride is added, and the mixture is then cooled to 22° C. and the pressure is released. The reaction mixture is filtered over Hyflo and, after evaporating off the ethanol, taken up in ethyl acetate. The ethyl acetate phase is washed with dilute hydrochloric acid and then with brine, dried over sodium sulfate, filtered and finally concentrated to dryness in vacuo. 3.17 g of a brown solid are obtained, which is purified by means of flash chromatography (silica gel; eluant: n-hexane/ethyl acetate 2/1 (v/v)). 2.31 g of the desired title compound are obtained in the form of a light-yellow solid having a melting point of 117-118° C.

Workup

  1. customAt 22° C.
  2. temperaturethe mixture is then cooled to 22° C.
  3. filtrationThe reaction mixture is filtered over Hyflo
  4. customafter evaporating off the ethanol
  5. washThe ethyl acetate phase is washed with dilute hydrochloric acid
  6. dry with materialwith brine, dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationfinally concentrated to dryness in vacuo

Sources & evidence

ORD record
ord-a3b7b706864943b2ad47ca38a4ed4692
Source dataset
uspto-grants-2001_08
Patent number
US06274536B1

Reaction notes

Loading…