4-Methoxybenzylamine → HCID 67404292, compound

HRID 333682Notes

Reaction equation

HRID 333682 reaction equation
C[C:2]([O-:5])(C)C.[Na+].Br[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1/[CH:14]=[C:15](\Br)/[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[CH3:23][O:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29][NH2:30])=[CH:27][CH:26]=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH3:23][O:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29][N:30]2[C:15]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:14][C:9]3[C:8](=[CH:13][CH:12]=[CH:11][CH:10]=3)[C:2]2=[O:5])=[CH:27][CH:26]=1

Participants

7

Reactant 3

HCID 754524-MethoxybenzylamineHCID 23676156Sodium t-butoxideHCID 86680978HCID 86680978, compound

Product 1

HCID 67404292HCID 67404292, compoundYield 54.9%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
55 °C

Procedure

NaOtBu (68.23 mg, 0.71 mmol, 3.0 eq.), Xantphos (6.8 mg, 0.012 mmol, 5 mol %), Pd2 dba3 (10.8 mg, 0.012 mmol, 5 mol %) are added to a flask dried under vacuum. The reagents are dissolved in toluene distilled with CaH2 under argon (0.8 ml). The red solution is degassed under argon with sonication for 30 seconds. A solution of (Z)-1-bromo-2-(2-bromo-2-phenylvinyl)benzene (80 mg, 0.24 mmol, 1.0 eq) and p-methoxybenzyl amine (114 mg, 0.83 mmol, 3.5 eq.) in toluene distilled with CaH2 under argon (0.8 ml) is added to the catalytic system. After addition, the reaction medium is degassed with argon, and stirred for 1 hour 30 minutes at 55° C. Then, the reaction medium is degassed with carbon monoxide (in a flask, 1 atm.) for 25 minutes at 55° C. Then, the reaction medium is stirred at 90° C. for 16 hours. After cooling down to a.t., the reaction medium is quenched with a 1N HCl solution (5 ml). The organic phases are extracted with dichloromethane (twice), washed with a saturated solution of NaCl (twice), dried over MgSO4 then concentrated under reduced pressure. The crude is then purified by silica gel chromatography (pentane/diethyl ether (7/3)) in order to obtain 2-(4-methoxybenzyl)-3-phenylisoquinolin-1(2H)-one (45 mg, yield=54%) in the form of a yellowish solid.

Workup

  1. customdried under vacuum
  2. dissolutionThe reagents are dissolved in toluene
  3. distillationdistilled with CaH2 under argon (0.8 ml)
  4. customThe red solution is degassed under argon with sonication for 30 seconds
  5. additionis added to the catalytic system
  6. additionAfter addition
  7. customthe reaction medium is degassed with argon
  8. customThen, the reaction medium is degassed with carbon monoxide (in a flask, 1 atm.) for 25 minutes at 55° C
  9. stirringThen, the reaction medium is stirred at 90° C. for 16 hours
  10. temperatureAfter cooling down
  11. custom, the reaction medium is quenched with a 1N HCl solution (5 ml)
  12. extractionThe organic phases are extracted with dichloromethane (twice),
  13. washwashed with a saturated solution of NaCl (twice),
  14. dry with materialdried over MgSO4
  15. concentrationthen concentrated under reduced pressure
  16. customThe crude is then purified by silica gel chromatography (pentane/diethyl ether (7/3)) in order

Sources & evidence

ORD record
ord-3c42395eaf494ecea1a391f3d1df2bd9
Source dataset
uspto-grants-2014_11
Patent number
US08883763B2

Reaction notes

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