Triethylamine → Trifluoroacetic acid

HRID 1508529Notes

Reaction equation

HRID 1508529 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][NH2:10])=[CH:5][CH:4]=1.C(O[CH:14]=[C:15]([C:21](=[O:26])[C:22]([F:25])([F:24])[F:23])[C:16]([O:18][CH2:19][CH3:20])=[O:17])C.C(N(CC)CC)C>C(#N)C>[C:21]([OH:26])([C:22]([F:25])([F:24])[F:23])=[O:2].[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:21]([C:22]([F:23])([F:24])[F:25])=[C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:14]=[N:10]2)=[CH:5][CH:4]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 77023(4-Methoxyphenyl)hydrazineHCID 4685753Ethyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutanoate

Product 2

HCID 6422Trifluoroacetic acidHCID 13812946Ethyl 1-(4-methoxyphenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

4-Methoxy phenylhydrazine (1 g, 7.24 mmol) and ethyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutyrate (1.408 ml, 7.24 mmol) were stirred in acetonitrile (40 mL) at room temperature. To this mixture was added triethylamine (1.0 mL, 7.24 mmol). LCMS trace of aliquot taken immediately after the addition indicated completion of reaction. The crude mixture was further aged for 1 hr. Volatiles were removed under reduce pressure. The resulting crude mixture was purified by flash chromatography (SiO2, Isolute Flash Si; 100 g). The column was eluted by an EtOAc/hexanes mixture (0% to 20%). Related fractions were pooled and evaporated to afford a yellow oil of 1.4015 g. This oil was further purified by preparative HPLC (reverse phase, Kromasil® 100-5C18, 100×21.1 mm) eluting with acetonitrile/water+0.1% TFA (30% to 100% organic in 10 min, then to 100% for 2 min, 20 mL/min). Related fractions were pooled and evaporated under reduced pressure to afford an oil as a TFA salt of the titled compound.

Workup

  1. additionafter the addition
  2. customcompletion of reaction
  3. customVolatiles were removed
  4. customThe resulting crude mixture was purified by flash chromatography (SiO2, Isolute Flash Si; 100 g)
  5. washThe column was eluted by an EtOAc/hexanes mixture (0% to 20%)
  6. customevaporated
  7. customto afford a yellow oil of 1.4015 g
  8. customThis oil was further purified by preparative HPLC (reverse phase, Kromasil® 100-5C18, 100×21.1 mm)
  9. washeluting with acetonitrile/water+0.1% TFA (30% to 100% organic in 10 min
  10. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-55b3f0ef554f47ab90723ddb4c840dbd
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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