Ammonium Acetate → 7-Chloro-6-fluoroisoquinolin-1(2H)-one

HRID 2370265Notes

Reaction equation

HRID 2370265 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:13])=[C:9]([Cl:12])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.C([O-])(=[O:16])C.[NH4+]>C(O)(=O)C>[Cl:12][C:9]1[CH:10]=[C:11]2[C:6]([CH:5]=[CH:4][NH:3][C:2]2=[O:16])=[CH:7][C:8]=1[F:13]

Participants

4

Reactant 2

HCID 517165Ammonium AcetateHCID 598182461,7-Dichloro-6-fluoroisoquinoline

Product 1

HCID 598182487-Chloro-6-fluoroisoquinolin-1(2H)-oneYield 39.5%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

41.13 g of 1,7-dichloro-6-fluoro-isoquinoline (6) were dissolved in 670 ml of acetic acid. After addition of 148.8 g of ammonium acetate, the solution was stirred at 100° C. After 3 h, the solvent was removed under reduced pressure and the residue was poured onto water. The aqueous phase was extracted three times with dichloromethane, the combined organic layer was washed with saturated sodium bicarbonate solution and brine, dried over sodium sulfate and evaporated to dryness. The crude product was crystallized from ethyl acetate:heptane to yield 14.85 g of the desired product. Another 4.5 g could be obtained upon evaporation and silica gel chromatography of the mother liquor.

Workup

  1. customthe solvent was removed under reduced pressure
  2. additionthe residue was poured onto water
  3. extractionThe aqueous phase was extracted three times with dichloromethane
  4. washthe combined organic layer was washed with saturated sodium bicarbonate solution and brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated to dryness
  7. customThe crude product was crystallized from ethyl acetate

Sources & evidence

ORD record
ord-421c71093c9844d2b35c97e00cc96767
Source dataset
uspto-grants-2014_04
Patent number
US08710077B2

Reaction notes

Loading…