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

HRID 1481136Notes

Reaction equation

HRID 1481136 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]([CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH:9]=2)=[O:4].CC1C=C(C)[N:28]=[C:27](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:27]#[N:28])[C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH:9]=2)=[O:4]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 46863890C16H22F6IN2PHCID 898128624-Hydroxy-7-phenethyl-isoquinoline-3-carboxylic acid methyl esterHCID 178418546HCID 178418546, compound

Product 1

HCID 898128711-Cyano-4-hydroxy-7-phenethyl-isoquinoline-3-carboxylic acid methyl esterYield 74.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Procedure

A mixture of 4-hydroxy-7-phenethyl-isoquinoline-3-carboxylic acid methyl ester (250 mg, 0.81 mmol) and bis(2,4,6-trimethylpyridine)iodine(I) hexafluorophosphate (1.05 g, 2.04 mmol) in CH2Cl2 (10 mL) was stirred at r.t. for 16 h, then diluted with CH2Cl2. 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 (150 mg, 1.62 mmol) and anhydrous DMF (8 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 (50 mL) and water (50 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 200 mg of the title compound as a light yellow solid. MS: (+) m/z 333.28 (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-86a6f91438f64307bc5be8ff03ea0c3f
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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