Butyl vinyl ether → 2-Acetyl-5-amino-3-trifluoromethylpyridine

HRID 545073Notes

Reaction equation

HRID 545073 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH:42]([O:44]CCCC)=[CH2:43].C([O-])(O)=O.[Na+]>CO.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:8][C:5]1[CH:4]=[C:3]([C:9]([F:12])([F:11])[F:10])[C:2]([C:42](=[O:44])[CH3:43])=[N:7][CH:6]=1

Participants

7

Reactant 4

HCID 8108Butyl vinyl etherHCID 812191,3-Bis(diphenylphosphino)propaneHCID 516892Sodium BicarbonateHCID 135322446-Chloro-5-(trifluoromethyl)pyridin-3-amine

Product 1

HCID 586455412-Acetyl-5-amino-3-trifluoromethylpyridine

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolvent

Procedure

Heat a mixture of 6-chloro-5-trifluoromethyl-pyridin-3-ylamine (985 mg, 5.0 mmol), palladium acetate (20 mg), DPPP (60 mg), butyl vinyl ether (1.5 g, 15 mmol) and NaHCO3 (840 mg, 10 mmol) in MeOH (10 mL) at 130° C. for 18 hours. Cool, filter and wash the solid with MeOH. Add 6M hydrochloric acid (5 mL), stir for 1 hour and evaporate the volatiles. Dissolve the residue in EtOAc (50 mL) and wash with saturated NaHCO3(aq) (50 mL) and brine (50 mL). Dry the organic extract over MgSO4 and remove the solvent under reduced pressure to yield the title compound.

Workup

  1. temperatureHeat
  2. temperatureCool
  3. filtrationfilter
  4. washwash the solid with MeOH
  5. additionAdd 6M hydrochloric acid (5 mL)
  6. customevaporate the volatiles
  7. dissolutionDissolve the residue in EtOAc (50 mL)
  8. washwash with saturated NaHCO3(aq) (50 mL) and brine (50 mL)
  9. customDry the
  10. extractionorganic extract over MgSO4
  11. customremove the solvent under reduced pressure

Sources & evidence

ORD record
ord-b877ee99b58b40699f4e90532de82053
Source dataset
uspto-grants-2011_05
Patent number
US07935702B2

Reaction notes

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