Potassium Carbonate → HCID 57557431, compound

HRID 1522836Notes

Reaction equation

HRID 1522836 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[C:5](=[O:14])[N:4]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[C:29]1(B(O)O)[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>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>[CH3:13][O:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[C:5](=[O:14])[N:4]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=1)[CH:3]=[C:2]2[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 24962933HCID 24962933, compound

Product 1

HCID 57557431HCID 57557431, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

4-Bromo-6-methoxy-2-(4-methoxyphenyl)-isoquinolin-1(2H)-one (0.52 g, 1.44 mmol), tetrakis(triphenylphosphine)palladium (83 mg, 0.07 mmol), potassium carbonate (0.22 g, 1.00 mmol) and phenylboronic acid (0.21 g, 1.73 mmol) were placed in a dry and argon flushed 150 mL three-necked round-bottomed flask fitted with a stirring bar and reflux condenser. 1,2-Dimethoxyethane (10 mL) and water (3 mL) were added via a syringe under argon atmosphere. The reaction solution was stirred and heated to reflux for 20 hours. The reaction was quenched by adding 30 mL of water at room temperature. The mixture was extracted with ethyl acetate (3×20 mL). The extracts were combined, washed with brine (2×10 mL) and dried over anhydrous MgSO4 and 2 g of 3-(diethylenetriamino)propylfunctionalized silica gel followed by filtration and concentration to give a yellow residue. The yellow residue was purified by flash column chromatography (silica-gel, hexanes/ethyl acetate=2/3 v/v) to give a white solid product, 0.50 g, 98.0% yield. MS: m/z 358.3 [M+H]+. 1H NMR (DMSO-d6, 300 MHz) (8.30 (d, 2H, J=9.0 Hz), 7.55-7.40 (m, 8H), 7.29 (s, 1H), 7.21 (dd, 1H, J1=9.0 Hz, J2=2.4 Hz), 7.05 (d, 2H, J=9.0 Hz), 6.94 (d, 1H, J=2.4 Hz), 3.81 (s, 3H), 3.78 (s, 3H).

Workup

  1. customa dry
  2. customargon flushed 150 mL three-necked round-bottomed flask
  3. customfitted with a stirring bar
  4. temperaturereflux condenser
  5. addition1,2-Dimethoxyethane (10 mL) and water (3 mL) were added via a syringe under argon atmosphere
  6. temperatureheated
  7. temperatureto reflux for 20 hours
  8. customThe reaction was quenched
  9. additionby adding 30 mL of water at room temperature
  10. extractionThe mixture was extracted with ethyl acetate (3×20 mL)
  11. washwashed with brine (2×10 mL)
  12. dry with materialdried over anhydrous MgSO4 and 2 g of 3-(diethylenetriamino)propylfunctionalized silica gel
  13. filtrationfollowed by filtration and concentration
  14. customto give a yellow residue
  15. customThe yellow residue was purified by flash column chromatography (silica-gel, hexanes/ethyl acetate=2/3 v/v)
  16. customto give a white solid product, 0.50 g, 98.0% yield

Sources & evidence

ORD record
ord-959913a2a39243c3b97f37dd3d10a5c5
Source dataset
uspto-grants-2015_07
Patent number
US09078888B2

Reaction notes

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