Sodium Carbonate → Methyl 7-(4-hydroxyphenyl)-3-isoquinolinecarboxylate

HRID 2423405Notes

Reaction equation

HRID 2423405 reaction equation
FC(F)(F)S(O[C:7]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:17]([O:19][CH3:20])=[O:18])[N:13]=[CH:14]2)=[CH:9][CH:8]=1)(=O)=O.[OH:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC>[OH:23][C:24]1[CH:29]=[CH:28][C:27]([C:7]2[CH:16]=[C:15]3[C:10]([CH:11]=[C:12]([C:17]([O:19][CH3:20])=[O:18])[N:13]=[CH:14]3)=[CH:9][CH:8]=2)=[CH:26][CH:25]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27343604-Hydroxyphenylboronic acidHCID 59321500Methyl 7-(trifluoromethylsulfonyloxy)isoquinoline-3-carboxylate

Product 1

HCID 59321463Methyl 7-(4-hydroxyphenyl)-3-isoquinolinecarboxylateYield 46%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
50 °C

Procedure

A suspension of 38 g (113 mmol) of methyl 7-{[(trifluoromethyl)sulfonyl]oxy}-3-isoquinolinecarboxylate, 23.4 g (170 mmol) of (4-hydroxyphenyl)boronic acid, 6.54 g (5.67 mmol) of tetrakistriphenylphosphine palladium(0) and 200 mL of 2.0 M Na2CO3 (aq) in 700 mL of 1,2-dimethoxyethane was stirred at 50° C. for 90 min. The suspension was filtered through a pad of Celite® and the filter cake was washed with EtOAc. The combined organics were washed with water. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water and brine before being dried with Na2SO4, filtered and concentrated. Ethyl acetate was added and the mixture was stirred and heated. The mixture was filtered and the concentrated filtrate was purified by silica gel chromatography (eluting with 0-20% acetone in CH2Cl2). Fractions containing the product were combined and concentrated and combined with the solid which had been collected by filtration to give 14.50 g (46%) of methyl 7-(4-hydroxyphenyl)-3-isoquinolinecarboxylate. 1H NMR (400 MHz, DMSO-d6): δ 9.75 (s, 1H), 9.38 (s, 1H), 8.42 (s, 1H), 8.23 (s, 1H), 8.21 (d, J=8 Hz, 1H), 8.15 (d, J=8 Hz, 1H), 7.72 (d, J=9 Hz, 2H), 6.91 (d, J=9 Hz, 2H), 3.91 (s, 3H). ESI-LCMS m/z 280 (M+H)+.

Workup

  1. filtrationThe suspension was filtered through a pad of Celite®
  2. washthe filter cake was washed with EtOAc
  3. washThe combined organics were washed with water
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. washThe combined organic layers were washed with water and brine
  6. dry with materialbefore being dried with Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. additionEthyl acetate was added
  10. stirringthe mixture was stirred
  11. temperatureheated
  12. filtrationThe mixture was filtered
  13. customthe concentrated filtrate was purified by silica gel chromatography (eluting with 0-20% acetone in CH2Cl2)
  14. additionFractions containing the product
  15. concentrationconcentrated
  16. filtrationhad been collected by filtration

Sources & evidence

ORD record
ord-532837b537bc4f318dfe73aaa3ab3d4e
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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