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

HRID 2063889Notes

Reaction equation

HRID 2063889 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-4b08c483ba39488686e16d5c5514db33
Source dataset
uspto-grants-2012_10
Patent number
US08288390B2

Reaction notes

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