Methylhydrazine → ethyl 1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

HRID 2425555Notes

Reaction equation

HRID 2425555 reaction equation
C(O[CH:4]=[C:5]([C:11](=O)[C:12]([F:15])([F:14])[F:13])[C:6]([O:8][CH2:9][CH3:10])=[O:7])C.[CH3:17][NH:18][NH2:19].C(OCC)(=O)C.CCCCCCC>C(O)C.ClCCl>[CH3:17][N:18]1[C:11]([C:12]([F:15])([F:14])[F:13])=[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH:4]=[N:19]1

Participants

6

Reactant 3

HCID 6061MethylhydrazineHCID 4685753Ethyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutanoateHCID 21899848Ethylacetate heptane

Product 1

HCID 2737211ethyl 1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxylateYield 62%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Ethyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutanoate (10 g, 0.042 mole) was dissolved in ethanol (120 ml) and cooled to 0° C. Methyl hydrazine (2.11 g, 0.046 mole) (pre-stirred in concentrated HCl (4 ml)-EtOH (4 ml), 0° C., 30 min) in EtOH (20 ml) was added at 0° C., and the resulting solution was stirred at room temperature for 18 h. The yellow solution was evaporated and the residue suspended in water and basified with sodium carbonate solution (saturated) and extracted with ethyl acetate (3×30 ml). The organic layer was separated and back-washed with brine (2×30 ml). The organic layer was separated, dried (Na2SO4), filtered and evaporated to give an oil. Yield 7 g. 1H NMR (300 MHz, CDCl3) shows 6:1 for desired regioisomer. The oil was dissolved in dichloromethane and purified using an ISCO Companion (70 g silica col., heptane to ethyl acetate:heptane 1:1). The appropriate fractions were combined and evaporated to give a colourless oil, 5.71 g, Yield 62%. 1H NMR (400 MHz, CDCl3) δ 7.91 (s, 1H) 4.36, 4.34, 4.32, 4.30 (q, 2H) 4.08 (s, 3H) 1.38, 1.36, 1.34 (t, 3H). MS (ESI): m/z 223 (M+H)+. LC-MS ELSD 100% m/z 223 (M+H)+. TLC Ethyl acetate:heptane 1:1 0.7 UV+ve

Workup

  1. customThe yellow solution was evaporated
  2. extractionextracted with ethyl acetate (3×30 ml)
  3. customThe organic layer was separated
  4. washback-washed with brine (2×30 ml)
  5. customThe organic layer was separated
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated
  9. customto give an oil
  10. custompurified
  11. customevaporated
  12. customto give a colourless oil, 5.71 g, Yield 62%

Sources & evidence

ORD record
ord-28a9d8436df8413dbb8a4018f562dbe6
Source dataset
uspto-grants-2011_06
Patent number
US07964732B2

Reaction notes

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