Hydrogen Bromide → 2,2,4,6-Tetramethyl-5-[4-(4-methylphenyl)piperazin-1-yl]-2,3-dihydro-1-benzofuran-7-ol

HRID 1850479Notes

Reaction equation

HRID 1850479 reaction equation
C[O:2][C:3]1[C:11]2[O:10][C:9]([CH3:13])([CH3:12])[CH2:8][C:7]=2[C:6]([CH3:14])=[C:5]([N:15]2[CH2:20][CH2:19][N:18]([C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=3)[CH2:17][CH2:16]2)[C:4]=1[CH3:28].Br.C(=O)([O-])O.[Na+]>C(O)(=O)C>[CH3:12][C:9]1([CH3:13])[CH2:8][C:7]2[C:6]([CH3:14])=[C:5]([N:15]3[CH2:16][CH2:17][N:18]([C:21]4[CH:22]=[CH:23][C:24]([CH3:27])=[CH:25][CH:26]=4)[CH2:19][CH2:20]3)[C:4]([CH3:28])=[C:3]([OH:2])[C:11]=2[O:10]1

Participants

5

Reactant 3

HCID 260Hydrogen BromideHCID 516892Sodium BicarbonateHCID 594850811-(7-Methoxy-2,2,4,6-tetramethyl-2,3-dihydro-1-benzofuran-5-yl)-4-(4-methylphenyl)piperazine

Product 1

HCID 594849982,2,4,6-Tetramethyl-5-[4-(4-methylphenyl)piperazin-1-yl]-2,3-dihydro-1-benzofuran-7-olYield 16.4%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

To 1-(7-methoxy-2,2,4,6-tetramethyl-2,3-dihydro-1-benzofuran-5-yl)-4-(4-methylphenyl)piperazine (444 mg, 1.18 mmol) synthesized in Example 62, acetic acid (7 mL) and 48% aqueous solution of hydrobromic acid (7 ml) were added, followed by stirring at 100° C. for 12 hours. After cooling to room temperature, aqueous solution of saturated sodium hydrogen carbonate was added to the mixture solution, and then the mixture solution was extracted with ethyl acetate. The extract solution was 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 100:0-90:10) and the resulting solids were recrystallized from hexane-ethyl acetate to obtain the title compound 71.0 mg (yield 16%). Melting point was 185 to 189° C.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionthe mixture solution was extracted with ethyl acetate
  3. dry with materialThe extract solution was dried over anhydrous magnesium sulfate
  4. customThe solvent was removed by distillation under reduced pressure
  5. customThe resulting residue was purified by silica gel column chromatography (hexane-ethyl acetate 100:0-90:10)
  6. customthe resulting solids were recrystallized from hexane-ethyl acetate

Sources & evidence

ORD record
ord-c85ccda7f1834e6a8474a32b9bbb6e98
Source dataset
uspto-grants-2015_02
Patent number
US08957069B2

Reaction notes

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