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

HRID 1621291Notes

Reaction equation

HRID 1621291 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

41.1 g 1,7-dichloro-6-fluoro-isoquinoline (59) 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 into 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. The precipitate was filtered and dried to yield 9.91 g (83%) of the title compound. Rt=1.33 min (Method B). Detected mass: 198.0 (M+H+).

Workup

  1. customthe solvent was removed under reduced pressure
  2. additionthe residue was poured into 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-ef5dbf57dbfb41d2a00eb2d08ccaa842
Source dataset
uspto-grants-2014_07
Patent number
US08772492B2

Reaction notes

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