Pyridine → 3,4-Difluoro-2-(2-fluoro-4-iodoanilino)benzoyl fluoride

HRID 605668Notes

Reaction equation

HRID 605668 reaction equation
[F:1][C:2]1[C:3]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([I:19])=[CH:15][C:14]=2[F:20])=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5](O)=[O:6].N1C=CC=CC=1.N1C(F)=NC(F)=NC=1[F:29]>ClCCl.O>[F:1][C:2]1[C:3]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([I:19])=[CH:15][C:14]=2[F:20])=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([F:29])=[O:6]

Participants

6

Reactant 3

HCID 1049PyridineHCID 12664Cyanuric fluorideHCID 220256632-(2-Fluoro-4-iodoanilino)-3,4-difluorobenzoic acid

Product 1

HCID 594691583,4-Difluoro-2-(2-fluoro-4-iodoanilino)benzoyl fluorideYield 97.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred mixture of 3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzoic acid (12 g, 30.5 mmol), prepared using procedures similar to those described in U.S. Pat. No. 7,019,033, in dichloromethane (70 mL) at 0° C. was added pyridine (2.5 mL, 30.8 mmol) followed by dropwise addition of cyanuric fluoride (2.8 mL, 33.6 mmol). The reaction mixture was stirred at 0° C. for 10 minutes and then warmed to room temperature and stirred for 2 hours. The reaction mixture was diluted with water and extracted with dichloromethane (100 mL). The aqueous layer was extracted once with dichloromethane (50 mL). The combined organic layers were washed with saturated aqueous sodium bicarbonate solution, brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give crude product as a brownish solid. Crude product was purified by flash chromatography (plug, 25% ethyl acetate in hexanes) to afford 3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzoyl fluoride as a beige solid (11.8 g, 97% yield). 1H NMR (400 MHz, CD3OD): 8.41 (s, 1H), 7.80-7.81 (m, 1H), 7.52 (dd, 1H), 7.43-7.47 (m, 1H), 6.96-7.03 (m, 1H), 6.85-6.92 (m, 1H).

Workup

  1. customprepared
  2. temperaturewarmed to room temperature
  3. stirringstirred for 2 hours
  4. extractionextracted with dichloromethane (100 mL)
  5. extractionThe aqueous layer was extracted once with dichloromethane (50 mL)
  6. washThe combined organic layers were washed with saturated aqueous sodium bicarbonate solution, brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customto give crude product as a brownish solid
  10. customCrude product was purified by flash chromatography (plug, 25% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-5cbdadbb9def48779497286702d1cf92
Source dataset
uspto-grants-2011_03
Patent number
US07915250B2

Reaction notes

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