Sulfuric Acid → Ethyl 1-(3-fluoro-5-iodo-4-methoxyphenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

HRID 1508532Notes

Reaction equation

HRID 1508532 reaction equation
S(=O)(=O)(O)O.[F:6][C:7]1[CH:8]=[C:9]([N:15]2[C:19]([C:20]([F:23])([F:22])[F:21])=[C:18]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH:17]=[N:16]2)[CH:10]=[CH:11][C:12]=1[O:13][CH3:14].C1C(=O)N([I:36])C(=O)C1>C(O)(=O)C>[F:6][C:7]1[CH:8]=[C:9]([N:15]2[C:19]([C:20]([F:23])([F:22])[F:21])=[C:18]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH:17]=[N:16]2)[CH:10]=[C:11]([I:36])[C:12]=1[O:13][CH3:14]

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 120273N-IodosuccinimideHCID 67517094ethyl 1-(3-fluoro-4-methoxyphenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Product 1

HCID 67517199Ethyl 1-(3-fluoro-5-iodo-4-methoxyphenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Sulfuric acid (3 mL) was added into a cold (ice bath) mixture of ethyl 1-(3-fluoro-4-methoxyphenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (500 mg, 1.505 mmol) and NIS (339 mg, 1.505 mmol) in acetic acid (10 mL). The resulting mixture was stirred in an ice bath and was allowed to warm to ambient temperature overnight. The reaction was then heated in a 55° C. oil bath for 5 hrs. The crude mixture was combined with the reaction crude from an identical probe reaction (32 mg scale). The combined crude was poured into an ice/water mixture and extracted with EtOAc. The separated organic phase was dried over Na2SO4, filtered and evaporated to afford a dark mixture. This dark mixture was purified by flash chromatography (SiO2, Biotage SNAP Cartridge, silica gel, KP-Sil, 100 g cartridge). The column was eluted by an EtOAc/hexanes mixture (0% to 30%). Related fractions were pooled and evaporated to afford a colorless oil as the titled compound. LCMS calc.=457.98. found=459.06 (M+H)+.

Workup

  1. temperatureThe reaction was then heated in a 55° C. oil bath for 5 hrs
  2. extractionextracted with EtOAc
  3. dry with materialThe separated organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated
  6. customto afford a dark mixture
  7. customThis dark mixture was purified by flash chromatography (SiO2, Biotage SNAP Cartridge, silica gel, KP-Sil, 100 g cartridge)
  8. washThe column was eluted by an EtOAc/hexanes mixture (0% to 30%)
  9. customevaporated

Sources & evidence

ORD record
ord-7c15bdd963bc4ac286b473e7a7782de3
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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