Dimethylformamide → 1-Cyano-4-hydroxy-8-phenoxy-isoquinoline-3-carboxylic acid methyl ester

HRID 706130Notes

Reaction equation

HRID 706130 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7](Br)[C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[CH:10][C:9]=2[O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:4].[Cu][C:25]#[N:26].CN(C)C=O.C(Cl)(Cl)Cl.C(O)(C)C>O>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([C:25]#[N:26])[C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[CH:10][C:9]=2[O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:4]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 21906603Chloroform isopropyl alcoholHCID 866170621-Bromo-4-hydroxy-8-phenoxy-isoquinoline-3-carboxylic acid methyl esterHCID 178418546HCID 178418546, compound

Product 1

HCID 671101071-Cyano-4-hydroxy-8-phenoxy-isoquinoline-3-carboxylic acid methyl esterYield 54.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 1-bromo-4-hydroxy-8-phenoxy-isoquinoline-3-carboxylic acid methyl ester (1.22 g, 3.3 mmol), copper(I) cyanide (585 mg, 6.6 mmol), and anhydrous dimethylformamide (16 mL) was refluxed for ten minutes before it was cooled to room temperature and diluted with water. To the resulting slurry was added a chloroform/isopropanol mixture (3:1, 150 mL). After stirring for 10 minutes the solid components were separated by filtration and discarded. The organic layer of the filtrate was washed with water, and brine before it was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel with a gradient of methanol and dichloromethane to give the title compound as a white solid (574 mg): 1H NMR (CDCl3, 200 MHz): δ=12.26 (s, 1H), 8.15 (m, 1H), 7.71 (t, J=8.2 Hz, 1H), 7.38 (m, 2H), 7.17 (m, 4H), 4.12 (s, 3H).

Workup

  1. temperaturewas refluxed for ten minutes before it
  2. customwere separated by filtration
  3. washThe organic layer of the filtrate was washed with water, and brine before it
  4. dry with materialwas dried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography on silica gel with a gradient of methanol and dichloromethane

Sources & evidence

ORD record
ord-9a26b6eaf1a84eef8eaface5a9ad5646
Source dataset
uspto-grants-2015_11
Patent number
US09174976B2

Reaction notes

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