Phosphorus oxychloride → 1,4-Dichloro-7-(3-cyanophenyl)isoquinoline

HRID 479566Notes

Reaction equation

HRID 479566 reaction equation
O=P(Cl)(Cl)[Cl:3].[Cl:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([C:23]#[N:24])[CH:18]=3)=[CH:14][CH:15]=2)[C:10](=O)[NH:9][CH:8]=1>CC#N>[Cl:3][C:10]1[C:11]2[C:16](=[CH:15][CH:14]=[C:13]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([C:23]#[N:24])[CH:18]=3)[CH:12]=2)[C:7]([Cl:6])=[CH:8][N:9]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 534397463-(4-Chloro-1-oxo-1,2-dihydroisoquinolin-7-YL)benzonitrile

Product 1

HCID 187712921,4-Dichloro-7-(3-cyanophenyl)isoquinolineYield 101.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

A solution of POCl3 (0.545 kg, 3.56 mol) in MeCN (0.76 L) was added to a suspension of 4-chloro-7-(3-cyanophenyl)isoquinolinone (0.50 kg, 1.78 mol) in boiling MeCN (4.25 L) under N2 over 1 hour. The mixture was heated at reflux overnight and then cooled to room temperature. The solid was collected by filtration, washed with MeCN (0.5 L) and dried in vacuo at 70° C. to give 1,4-dichloro-7-(3-cyanophenyl)isoquinoline (0.54 kg) as a creamy coloured solid which could be used without further drying or purification. The filtrate was slowly quenched with HCl (1N; 2.6 mL) which gave a second crop of 60 g of material which was filtered and washed with MeCN (0.5 L), which again could be used without further drying or purification.

Workup

  1. customover 1 hour
  2. temperatureThe mixture was heated
  3. temperatureat reflux overnight
  4. filtrationThe solid was collected by filtration
  5. washwashed with MeCN (0.5 L)
  6. customdried in vacuo at 70° C.

Sources & evidence

ORD record
ord-c836a22dd9114d819d65be37b83f84c6
Source dataset
uspto-grants-2003_11
Patent number
US06645979B2

Reaction notes

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