Hydrochloric Acid → 4-Hydroxy-8-(4-methoxy-phenoxy)-isoquinoline-3-carboxylic acid methyl ester

HRID 409233Notes

Reaction equation

HRID 409233 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]=[CH:7][C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[CH:10][C:9]=2I)=[O:4].[CH3:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC(C)(C(=O)CC(=O)C(C)(C)C)C.Cl>Cl[Cu].O.C(OCC)(=O)C.CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[N:6]=[CH:7][C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[CH:10][C:9]=2[O:25][C:22]1[CH:23]=[CH:24][C:19]([O:18][CH3:17])=[CH:20][CH:21]=1)=[O:4]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 90154-MethoxyphenolHCID 10796Cesium carbonateHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 67110147Methyl 4-hydroxy-8-iodoisoquinoline-3-carboxylate

Product 1

HCID 671102494-Hydroxy-8-(4-methoxy-phenoxy)-isoquinoline-3-carboxylic acid methyl esterYield 10.3%

Reagents, catalysts & solvents 4

HCID 62652Cuprous chlorideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-Hydroxy-8-iodo-isoquinoline-3-carboxylic acid methyl ester (7 mmol, 2.3 g), 4-methoxy-phenol (35 mmol, 4.39 g), Cs2CO3 (35 mmol, 11.42 g), 2,2,6,6-tetramethyl-heptane-3,5-dione (2.8 mmol, 0.59 mL), CuCl (7 mmol, 0.70 g), and anhydrous DMF (42 mL) was refluxed under nitrogen with stirring for 15 min. before it was poured into ethyl acetate (700 mL). Water (700 mL) and 5 N hydrochloric acid (5 mL) were added and the mixture was stirred for 15 min. The organic phase was then separated and washed with water (2×700 mL) before it was dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel using hexanes:EtOAc=75:25 as the eluent gave the title compound as a tan solid (234 mg); MS-(+)-ion: M+1=326.4.

Workup

  1. temperaturewas refluxed under nitrogen
  2. stirringthe mixture was stirred for 15 min
  3. customThe organic phase was then separated
  4. washwashed with water (2×700 mL) before it
  5. dry with materialwas dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-1e22b5f676ba4c56bab1e04ae14ae284
Source dataset
uspto-grants-2014_06
Patent number
US08759373B2

Reaction notes

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