Pyridine → 5-Chloro-1H-indole-2-carbonyl fluoride

HRID 379015Notes

Reaction equation

HRID 379015 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([OH:13])=O)=[CH:5]2.N1C=CC=CC=1.N1C(F)=NC(F)=NC=1[F:22]>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([F:22])=[O:13])=[CH:5]2

Participants

5

Reactant 3

HCID 1049PyridineHCID 12664Cyanuric fluorideHCID 826935-Chloro-1H-indole-2-carboxylic acid

Product 1

HCID 225938745-Chloro-1H-indole-2-carbonyl fluoride

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

A solution of 5-chloro-1H-indole-2-carboxylic acid (10.0 g, 51.1 mmol) and pyridine (33.1 mmol) in acetonitrile was added to a solution of cyanuric fluoride (2.76 g, 20.4 mmol) in acetonitrile (total 340 mL) at 25° C. The reaction was followed by TLC on aliquots quenched with butylamine and appeared nearly complete at 1 hour. The mixture was poured onto ice, extracted with ether, dried (Na2SO4), and concentrated giving a solid which was used without purification (10.0 g, 99%). TLC of a butylamine-quenched aliquot showed some 5-chloroindole-2-carboxylic acid and the less polar N-butylamide. A sample was purified by chromatography on silica gel eluting with ethyl acetate-hexanes (50-100%) for characterization (16368-130-1).

Workup

  1. customquenched with butylamine
  2. additionThe mixture was poured onto ice
  3. extractionextracted with ether
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customgiving a solid which
  7. customwas used without purification (10.0 g, 99%)
  8. customTLC of a butylamine-quenched aliquot
  9. customA sample was purified by chromatography on silica gel eluting with ethyl acetate-hexanes (50-100%) for characterization (16368-130-1)

Sources & evidence

ORD record
ord-d5b3331c50964542b808b4b2db2d1cf3
Source dataset
uspto-grants-2001_10
Patent number
US06297269B1

Reaction notes

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