Sodium Carbonate → HCID 10253960, compound

HRID 915367Notes

Reaction equation

HRID 915367 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[N:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][C:15]=1[CH3:21])[C:8](OS(C(F)(F)F)(=O)=O)=[CH:7]2.[O:30]([C:37]1[CH:42]=[CH:41][C:40](B(O)O)=[CH:39][CH:38]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C1([As](C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.CCOCC.O.[Pd](Cl)Cl.C(#N)C.C(#N)C>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[N:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][C:15]=1[CH3:21])[C:8]([C:40]1[CH:41]=[CH:42][C:37]([O:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[CH:38][CH:39]=1)=[CH:7]2

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 11773TriphenylarsineHCID 27343774-Phenoxyphenylboronic acidHCID 86594618HCID 86594618, compound2×

Product 1

HCID 10253960HCID 10253960, compoundYield 63%

Reagents, catalysts & solvents 4

HCID 6093782Bis(acetonitrile)dichloropalladiumCatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of trifluoromethanesulfonic acid 8-chloro-2-(2,4-dimethylbenzyl)-1-oxo-1,2-dihydroisoquinolin-3-yl ester (61.9 mg, 0.14 mmol), 4-phenoxyphenylboronic acid (45.9 mg, 0.21 mmol), and triphenylarsine (17.6 mg, 57.5 μmol) in THF (0.7 mL) under a nitrogen atmosphere was treated with bis-(acetonitrile) palladium (II) chloride (4.6 mg, 17.7 μmol) and aqueous sodium carbonate solution (0.7 mL of a 2 M solution) with vigorous stirring at ambient temperature. After 90 minutes stirring at ambient temperature, TLC analysis showed only a trace of starting trifluoromethanesulfonic acid 8-chloro-2-(2,4-dimethylbenzyl)-1-oxo-1,2-dihydroisoquinolin-3-yl ester remaining. The reaction was diluted with ether (20 mL), and water (10 mL). The basic aqueous layer was extracted with ether (3×10 mL). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and conc. to afford a yellow semi-solid. The material was purified by silica gel column chromatography eluting with a gradient from 0% to 10% ethyl acetate/hexane. The main peak was collected to afford 8-chloro-2-(2,4-dimethylbenzyl)-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one (41 mg, 63% yield) as a brittle white foam contaminated with a small amount (<10%) of an impurity: 1H-NMR (400 MHz, CDCl3): δ 7.51-7.49 (2H, m), 7.41-7.34 (3H, m), 7.18-7.11 (3H, m),7.04-7.00 (2H, m), 6.94-6.84 (5H, m), 6.68 (1H, d, J=7.8 Hz), 6.42 (1H, s), 5.09 (2H, s), 2.24 (3H, s), 2.00 (3H, s) ppm.

Workup

  1. stirringAfter 90 minutes stirring at ambient temperature
  2. extractionThe basic aqueous layer was extracted with ether (3×10 mL)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customconc. to afford a yellow semi-solid
  7. customThe material was purified by silica gel column chromatography
  8. washeluting with a gradient from 0% to 10% ethyl acetate/hexane
  9. customThe main peak was collected

Sources & evidence

ORD record
ord-73d46d64bf914fa1a059a7ba89e172cd
Source dataset
uspto-grants-2007_09
Patent number
US07265131B2

Reaction notes

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