Hydrochloric Acid → 1-Cyano-4-hydroxy-7-phenyl-isoquinoline-3-carboxylic acid methyl ester

HRID 1481164Notes

Reaction equation

HRID 1481164 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]=[C:10]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH:9]=2)=[O:4].CC1C=C(C)[N:26]=[C:25](C)C=1.CC1C([IH+])=C(C)N=C(C)C=1.F[P-](F)(F)(F)(F)F.C([Cu])#N.Cl>C(Cl)Cl.O.CN(C=O)C>[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]=[C:10]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH:9]=2)=[O:4]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 46863890C16H22F6IN2PHCID 89812805HCID 89812805, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 898129441-Cyano-4-hydroxy-7-phenyl-isoquinoline-3-carboxylic acid methyl esterYield 50.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Procedure

A mixture of 4-hydroxy-7-phenyl-isoquinoline-3-carboxylic acid methyl ester (170 mg, 0.61 mmol) and bis(2,4,6-trimethylpyridine)iodine(I) hexafluorophosphate (783 mg, 1.52 mmol) in CH2Cl2 (10 mL) was stirred at r.t. for 16 h, then diluted with CH2Cl2 (50 mL). The resulting mixture was washed with 5% sodium thiosulfate and 1 M HCl. The organic layer was dried over MgSO4 and concentrated. To the residue were added CuCN (102 mg, 1.14 mmol) and anhydrous DMF (6 mL), and the resulting mixture was refluxed for 20 min. After cooling to r.t., the reaction mixture was poured into a mixture of CH2Cl2 (100 mL) and water (100 mL). 4 M HCl was added with vigorous stirring until no solid was observed. The aqueous layer was extracted with additional CH2Cl2, and the organic layers were combined, dried over MgSO4 and concentrated. The crude product was purified by column chromatography (20-100% CH2Cl2/hexanes) to give 93 mg of the title compound as a light brown solid. MS: (+) m/z 305.06 (M+1).

Workup

  1. washThe resulting mixture was washed with 5% sodium thiosulfate and 1 M HCl
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated
  4. temperaturethe resulting mixture was refluxed for 20 min
  5. temperatureAfter cooling to r.t.
  6. stirringwith vigorous stirring until no solid
  7. extractionThe aqueous layer was extracted with additional CH2Cl2
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customThe crude product was purified by column chromatography (20-100% CH2Cl2/hexanes)

Sources & evidence

ORD record
ord-5497e054f7a7463eab9ce17bac4762f0
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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