Tetrahydrofuran → 7-Benzyl-4-hydroxy-isoquinoline-3-carboxylic acid methyl ester

HRID 1481182Notes

Reaction equation

HRID 1481182 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]=[CH:7][C:8]2[C:13]([C:14]=1[O:15]CC1C=CC=CC=1)=[CH:12][CH:11]=[C:10](Br)[CH:9]=2)=[O:4].C1COCC1.[Br-].[CH2:30]([Zn+])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.[NH4+].[Cl-]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(Cl)Cl>[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]([CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH:9]=2)=[O:4]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 89812966Methyl 4-(benzyloxy)-7-bromoisoquinoline-3-carboxylateHCID 178419772HCID 178419772, compound

Product 1

HCID 671101307-Benzyl-4-hydroxy-isoquinoline-3-carboxylic acid methyl esterYield 16.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 4-benzyloxy-7-bromo-isoquinoline-3-carboxylic acid methyl ester (150 mg, 0.40 mmol), Pd(PPh3)4 (47 mg, 0.040 mmol) and THF (4 mL) was added benzylzinc bromide (2 mL, 1.0 mmol, 0.5 M in THF), and the resulting mixture was refluxed for 16 h under nitrogen atmosphere. After cooling the mixture to r.t., saturated NH4Cl (50 mL) and CH2Cl2 (50 mL) were added. The aqueous layer was extracted with additional CH2Cl2, and the organic layers were combined and dried over MgSO4. After evaporating the solvent, the crude product was purified by column chromatography (0-35% EtOAc/hexanes) to give 19 mg of the title compound as a yellow solid. MS: (+) m/z 294.05 (M+1).

Workup

  1. temperaturethe resulting mixture was refluxed for 16 h under nitrogen atmosphere
  2. extractionThe aqueous layer was extracted with additional CH2Cl2
  3. dry with materialdried over MgSO4
  4. customAfter evaporating the solvent
  5. customthe crude product was purified by column chromatography (0-35% EtOAc/hexanes)

Sources & evidence

ORD record
ord-a493c1928ac64963a29527eec1608833
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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