Dimethylformamide → 1-Cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid butyl ester

HRID 706123Notes

Reaction equation

HRID 706123 reaction equation
[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10](Br)[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[C:13]([O:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4].[C:27]([Cu])#[N:28].CN(C)C=O>C(OCC)(=O)C>[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10]([C:27]#[N:28])[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[C:13]([O:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 86595463Butyl 1-bromo-4-hydroxy-7-phenoxyisoquinoline-3-carboxylateHCID 178418546HCID 178418546, compound

Product 1

HCID 671101111-Cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid butyl esterYield 57.6%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1-bromo-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid butyl ester (624 mg, 1.5 mmol; prepared as shown in Scheme 2, and according to US 2004/0254215 A1, 1H NMR (CDCl3): δ=11.89 (s, 1H), 8.35 (d, 1H), 7.63 (d, 1H), 7.08 to 7.52 (m, 6H), 4.47 (t, 2H), 1.84 (m, 2H), 1.48 (m, 2H), 0.99 (t, 3H)), CuCN (271 mg, 3 mmol) and dimethylformamide (6 mL) was refluxed with stirring under nitrogen for 15 min. After cooling to ambient temperature the mixture was diluted with ethyl acetate (100 mL). The resulting suspension was filtered through a pad of celite. The filtrate was washed with water (2×250 mL), and dried over MgSO4 before silica gel was added. Subsequently, the mixture was concentrated in vacuo. The residue was added on top of a short column filled with silica gel. Elution with dichloromethane gave the title compound as a white solid (313 mg); MS-(−)-ion: M−1=361.2.

Workup

  1. temperaturewas refluxed
  2. filtrationThe resulting suspension was filtered through a pad of celite
  3. washThe filtrate was washed with water (2×250 mL)
  4. dry with materialdried over MgSO4 before silica gel
  5. additionwas added
  6. concentrationSubsequently, the mixture was concentrated in vacuo
  7. additionThe residue was added on top of a short column
  8. additionfilled with silica gel
  9. washElution with dichloromethane

Sources & evidence

ORD record
ord-4dce14405b8b4d30b2d398fb9f594adb
Source dataset
uspto-grants-2015_11
Patent number
US09174976B2

Reaction notes

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