Dimethylacetamide → 7-Benzyloxy-1-cyano-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester

HRID 409330Notes

Reaction equation

HRID 409330 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8](Br)[C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[C:11]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH:10]=2)=[O:5])[CH3:2].[CH3:26][N:27](C)C(=O)C>C(OCC)(=O)C.[Cl-].[NH4+].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Zn].[C-]#N.[Zn+2].[C-]#N>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([C:26]#[N:27])[C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[C:11]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH:10]=2)=[O:5])[CH3:2]

Participants

9

Reactant 2

HCID 31374DimethylacetamideHCID 866170887-Benzyloxy-1-bromo-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester

Product 1

HCID 671102297-Benzyloxy-1-cyano-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester

Reagents, catalysts & solvents 6

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Procedure

7-Benzyloxy-1-cyano-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester was prepared by heating a mixture of 1.76 g (4.4 mmol) of 7-benzyloxy-1-bromo-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester, 201 mg (0.2.0 mmol) tris(dibenzylideneacetone)dipalladium(0), 243 mg (0.44 mmol) 1,1′-bis(diphenylphosphino) ferrocene, 34 mg (0.53 mmol) zinc dust, 309 mg (2.64 mmol) zinc cyanide, and 9.0 mL of N,N-dimethylacetamide at 115 deg C. for 3 hours. The resultant mixture was diluted with ethyl acetate and saturated aqueous ammonium chloride and filtered through a celite pad. The organic fraction was washed with saturated ammonium chloride, water, brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by flash chromatography, eluting from silica gel with a 10 to 90 percent gradient of ethyl acetate in hexanes to give 1.18 g of the title compound; MS (ESI+): 349.3 e/z (M+1)

Workup

  1. custom7-Benzyloxy-1-cyano-4-hydroxy-isoquinoline-3-carboxylic acid ethyl ester was prepared
  2. temperatureby heating
  3. filtrationfiltered through a celite pad
  4. washThe organic fraction was washed with saturated ammonium chloride, water, brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography
  8. washeluting from silica gel with a 10 to 90 percent gradient of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-5e8fdc03c26d4e13a4071163b7129da0
Source dataset
uspto-grants-2014_06
Patent number
US08759373B2

Reaction notes

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