4-Bromo-1-methoxy-2-methylbenzene → HCID 66760999, compound

HRID 2063798Notes

Reaction equation

HRID 2063798 reaction equation
CC(C)([O-])C.[Na+].[CH3:7][C:8]1([CH3:27])[C:12](=[O:13])[C:11]2[C:14]([CH3:26])=[C:15]([N:20]3[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)[C:16]([CH3:19])=[C:17]([CH3:18])[C:10]=2[O:9]1.Br[C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[C:31]([CH3:37])[CH:30]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH3:36][O:35][C:32]1[CH:33]=[CH:34][C:29]([N:23]2[CH2:22][CH2:21][N:20]([C:15]3[C:16]([CH3:19])=[C:17]([CH3:18])[C:10]4[O:9][C:8]([CH3:27])([CH3:7])[C:12](=[O:13])[C:11]=4[C:14]=3[CH3:26])[CH2:25][CH2:24]2)=[CH:30][C:31]=1[CH3:37]

Participants

8

Reactant 4

HCID 6083154-Bromo-1-methoxy-2-methylbenzeneHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 66759817HCID 66759817, compound

Product 1

HCID 66760999HCID 66760999, compoundYield 23%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

Sodium t-butoxide (999 mg, 10.4 mmol) was added to a mixture of toluene (18 mL) containing 2,2,4,6,7-pentamethyl-5-piperazin-1-yl-1-benzofuran-3(2H)-one (1.00 g, 3.47 mmol) synthesized in Reference Example 58, 4-bromo-2-methylanisole (2.09 g, 10.4 mmol), palladium acetate (39 mg, 0.174 mmol) and BINAP (325 mg, 0.522 mmol), and the mixture was stirred under heated reflux for 15 hours. After cooled to room temperature, the reaction solution was diluted with water and extracted using ethyl acetate. The organic layer was washed with saturated saline, and then dried using anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the obtained residue was purified by silica gel chromatography (hexane-ethyl acetate 95:5 to 85:15). Crystallization was performed using ethyl acetate-hexane to give 320 mg of the title compound (yield: 23%).

Workup

  1. temperatureunder heated
  2. temperaturereflux for 15 hours
  3. extractionextracted
  4. washThe organic layer was washed with saturated saline
  5. customdried
  6. customThe solvent was removed under reduced pressure
  7. customthe obtained residue was purified by silica gel chromatography (hexane-ethyl acetate 95:5 to 85:15)
  8. customCrystallization

Sources & evidence

ORD record
ord-364e47c7624a4123ae7b125b2129a16f
Source dataset
uspto-grants-2012_10
Patent number
US08288390B2

Reaction notes

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