4-Bromo-1-methoxy-2-methylbenzene → HCID 59485110, compound

HRID 1850432Notes

Reaction equation

HRID 1850432 reaction equation
[CH3:1][CH:2]1[CH2:6][C:5]2[C:7]([CH3:19])=[C:8]([N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)[C:9]([CH3:12])=[C:10]([CH3:11])[C:4]=2[O:3]1.Br[C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[C:23]([CH3:29])[CH:22]=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.CC(C)([O-])C.[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[CH3:28][O:27][C:24]1[CH:25]=[CH:26][C:21]([N:16]2[CH2:15][CH2:14][N:13]([C:8]3[C:9]([CH3:12])=[C:10]([CH3:11])[C:4]4[O:3][CH:2]([CH3:1])[CH2:6][C:5]=4[C:7]=3[CH3:19])[CH2:18][CH2:17]2)=[CH:22][C:23]=1[CH3:29]

Participants

8

Reactant 4

HCID 6083154-Bromo-1-methoxy-2-methylbenzeneHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 667598101-(2,4,6,7-Tetramethyl-2,3-dihydro-1-benzofuran-5-yl)piperazine

Product 1

HCID 59485110HCID 59485110, compoundYield 19.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To the toluene (3.1 mL) solution of 1-(2,4,6,7-tetramethyl-2,3-dihydro-1-benzofuran-5-yl)piperazine (400 mg, 1.54 mmol) synthesized in Reference example 56, 4-bromo-1-methoxy-2-methylbenzene (464 mg, 2.31 mmol), palladium acetate (17 mg, 0.077 mmol), BINAP (143 mg, 0.231 mmol) and sodium tert-butoxide (296 mg, 3.08 mmol) were added and irradiated with microwave. The mixture was reacted for 15 minutes at 150° C. To the mixture solution, water was added and extracted with ethyl acetate. The extract solution was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate 85:15). The resulting solid was recrystallized from ethanol to obtain the title compound 114 mg (yield 19%). Melting point was 141 to 142° C. (ethanol).

Workup

  1. additionwere added
  2. customirradiated with microwave
  3. customThe mixture was reacted for 15 minutes at 150° C
  4. extractionextracted with ethyl acetate
  5. washThe extract solution was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was removed by distillation under reduced pressure
  8. customThe resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate 85:15)
  9. customThe resulting solid was recrystallized from ethanol

Sources & evidence

ORD record
ord-7f791769dc5a452eb8a7f903320fc9ac
Source dataset
uspto-grants-2015_02
Patent number
US08957069B2

Reaction notes

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