Toluene → 7-Chloro-5-(4-methoxy-benzyloxy)-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one

HRID 2427539Notes

Reaction equation

HRID 2427539 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].C1(C)C=CC=CC=1.Br[C:15]1[CH:16]=[C:17]2[C:21](=[C:22]([Cl:24])[CH:23]=1)[C:20](=[O:25])[N:19]([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][C:34]([F:37])([F:36])[F:35])=[CH:29][CH:28]=1)[CH2:18]2.[CH3:38][O:39][C:40]1[CH:47]=[CH:46][C:43]([CH2:44][OH:45])=[CH:42][CH:41]=1>C(OCC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(P(C(C)(C)C)C1C=CC2C(=CC=CC=2)C=1C1C2C(=CC=CC=2)C=CC=1)(C)(C)C>[Cl:24][C:22]1[CH:23]=[C:15]([O:45][CH2:44][C:43]2[CH:46]=[CH:47][C:40]([O:39][CH3:38])=[CH:41][CH:42]=2)[CH:16]=[C:17]2[C:21]=1[C:20](=[O:25])[N:19]([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][C:34]([F:37])([F:36])[F:35])=[CH:29][CH:28]=1)[CH2:18]2

Participants

8

Reactant 4

HCID 1140TolueneHCID 77384-Methoxybenzyl alcoholHCID 10796Cesium carbonateHCID 117044755-Bromo-7-chloro-2-(4-trifluoromethoxybenzyl)-2,3-dihydroisoindol-1-one

Product 1

HCID 579494297-Chloro-5-(4-methoxy-benzyloxy)-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-oneYield 37%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 2734941(1,1'-Binaphthalen)-2-yldi-tert-butylphosphineCatalystHCID 3283Diethyl EtherSolvent

Conditions

Temperature
95 °C

Procedure

Palladium acetate (0.54 mg, 0.0024 mmol), racemic-2-(di-t-butylphosphino)-1,1′-binaphthyl (1.2 mg, 0.003 mmol), and cesium carbonate (58.6 mg, 0.18 mmol) were added to a vial and the vial was filled with Argon. Toluene (1.5 mL) was added and the vial was degassed with a pump and filled again with Argon. 5-Bromo-7-chloro-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one (50.0 mg, 0.12 mmol) and 4-methoxy-benzyl alcohol (33.2 mg, 0.24 mmol) were added and the mixture was stirred at 95° C. for forty-five hours. The cooled mixture was then diluted with diethyl ether and filtered through Celite®. Column chromatography (20% EtOAc/Hexanes to 100% EtOAc) provided the title compound (21.1 mg, 37%).

Workup

  1. additionwas filled with Argon
  2. customthe vial was degassed with a pump
  3. additionfilled again with Argon
  4. filtrationfiltered through Celite®

Sources & evidence

ORD record
ord-15406fd3a7c4425cad1a9d2817a7283b
Source dataset
uspto-grants-2011_06
Patent number
US07968570B2

Reaction notes

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