Trifluoroacetic acid → ethyl 5-amino-1-(4-ethoxy-2,6-difluorobenzyl)-4-methyl-1H-pyrazole-3-carboxylate

HRID 1774530Notes

Reaction equation

HRID 1774530 reaction equation
[C:1](/[C:3](/[CH3:11])=[C:4](\[O-])/[C:5]([O:7][CH2:8][CH3:9])=[O:6])#[N:2].[K+].FC(F)(F)C(O)=O.Cl.Cl.[CH2:22]([O:24][C:25]1[CH:33]=[C:32]([F:34])[C:28]([CH2:29][NH:30][NH2:31])=[C:27]([F:35])[CH:26]=1)[CH3:23]>O1CCOCC1>[NH2:2][C:1]1[N:30]([CH2:29][C:28]2[C:27]([F:35])=[CH:26][C:25]([O:24][CH2:22][CH3:23])=[CH:33][C:32]=2[F:34])[N:31]=[C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:3]=1[CH3:11]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 24824588potassium (2Z)-3-cyano-1-ethoxy-1-oxobut-2-en-2-olateHCID 89647959(4-Ethoxy-2,6-difluorobenzyl)hydrazine dihydrochloride

Product 1

HCID 89662197ethyl 5-amino-1-(4-ethoxy-2,6-difluorobenzyl)-4-methyl-1H-pyrazole-3-carboxylate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

2.01 g potassium (2Z)-3-cyano-1-ethoxy-1-oxobut-2-en-2-olate (10.9 mmol, 1.0 eq.) were dissolved in dioxane at rt and 1.34 mL trifluoroacetic acid (17.4 mmol, 1.6 eq.) were added within 2 minutes. The slurry was stirred for 10 minutes and 3.00 g (4-ethoxy-2,6-difluorobenzyl)hydrazine dihydrochloride (10.9 mmol, 1.0 eq.) were added. The reaction mixture was stirred at 130° C. for 3 hours. The resulting solid was filtered off and washed rinsed with dioxane. The filtrate was partitioned between ethyl acetate and water. The aqueous phase was washed with ethyl acetate three times. The collected organic solutions were washed with brine, dried over a silicon filter, concentrated in vacuo and purified by flash chromatography: 1.10 g (2.42 mmol, 22%) of a 71% pure target compound.

Workup

  1. stirringThe reaction mixture was stirred at 130° C. for 3 hours
  2. filtrationThe resulting solid was filtered off
  3. washwashed
  4. washrinsed with dioxane
  5. customThe filtrate was partitioned between ethyl acetate and water
  6. washThe aqueous phase was washed with ethyl acetate three times
  7. washThe collected organic solutions were washed with brine
  8. customdried over a silicon
  9. filtrationfilter
  10. concentrationconcentrated in vacuo
  11. custompurified by flash chromatography

Sources & evidence

ORD record
ord-f9a65ab6be8d4f58960d8a2b8b146599
Source dataset
uspto-grants-2016_02
Patent number
US09260412B2

Reaction notes

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