Phosphorus oxychloride → 1-Chloro-8-fluoroisoquinoline-3-carbonitrile

HRID 1476814Notes

Reaction equation

HRID 1476814 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=O)[NH:9][C:8]([C:13]([NH2:15])=O)=[CH:7]2.O=P(Cl)(Cl)[Cl:18]>>[Cl:18][C:10]1[C:11]2[C:6](=[CH:5][CH:4]=[CH:3][C:2]=2[F:1])[CH:7]=[C:8]([C:13]#[N:15])[N:9]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 903872368-Fluoro-1-oxo-1,2-dihydroisoquinoline-3-carboxamide

Product 1

HCID 903868251-Chloro-8-fluoroisoquinoline-3-carbonitrileYield 281.6%

Procedure

A solution of 8-fluoro-1-oxo-1,2-dihydroisoquinoline-3-carboxamide (5 g, 5.5 mmol) in POCl3 (46.23 g) was heated to reflux for 4 hours and was subsequently concentrated in vacuo. The crude product was purified by column chromatography eluting with petroleum ether and ethyl acetate (PE/EtOAc=5:1-2:1 gradient) to give the title compound (3.2 g, 35%). ESI-MS m/z [M+H]+ 207.1.

Workup

  1. temperatureto reflux for 4 hours
  2. concentrationwas subsequently concentrated in vacuo
  3. customThe crude product was purified by column chromatography
  4. washeluting with petroleum ether and ethyl acetate (PE/EtOAc=5:1-2:1 gradient)

Sources & evidence

ORD record
ord-a4eedae3a167445c8bd66d1a3eb04350
Source dataset
uspto-grants-2016_08
Patent number
US09402841B2

Reaction notes

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