Sodium Hydroxide → 1-(4-Methoxyphenyl)-4-(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)piperazine

HRID 1850429Notes

Reaction equation

HRID 1850429 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl-].[Al+3].[Cl-].[Cl-].[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([N:19]2[CH2:24][CH2:23][N:22]([C:25]3[C:26]([CH3:39])=[C:27]([CH3:38])[C:28]4[O:32][C:31]([CH3:34])([CH3:33])[C:30](=O)[C:29]=4[C:36]=3[CH3:37])[CH2:21][CH2:20]2)=[CH:15][CH:14]=1.[OH-].[Na+]>O.C1COCC1>[CH3:11][O:12][C:13]1[CH:14]=[CH:15][C:16]([N:19]2[CH2:24][CH2:23][N:22]([C:25]3[C:26]([CH3:39])=[C:27]([CH3:38])[C:28]4[O:32][C:31]([CH3:33])([CH3:34])[CH2:30][C:29]=4[C:36]=3[CH3:37])[CH2:21][CH2:20]2)=[CH:17][CH:18]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 6451240Aluminum(III) ChlorideHCID 21226445Aluminium lithium hydrideHCID 229355955-[4-(4-methoxyphenyl)piperazin-1-yl]-2,2,4,6,7-pentamethyl-1-benzofuran-3(2H)-one

Product 1

HCID 469103861-(4-Methoxyphenyl)-4-(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)piperazineYield 83%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

That is, to the THF (20 mL) suspension of lithium aluminum hydride (577 mg, 15.2 mmol), aluminum chloride (2.03 g, 15.2 mmol) was added under ice cooling, and then the mixture was stirred for 10 minutes and added with the THF (25 mL) solution of 5-[4-(4-methoxyphenyl)piperazin-1-yl]-2,2,4,6,7-pentamethyl-1-benzofuran-3(2H)-on (2.00 g, 5.07 mmol), and the mixture was stirred for 2 hours under reflux. After cooling the reaction solution on ice, water and 0.5 N aqueous solution of sodium hydroxide were serially added thereto. The mixture was stirred for 1 hour at room temperature, and then extraction was performed using ethyl acetate. The extract was washed with saturated saline and dried over anhydrous magnesium sulfate. After that, the solvent was removed by distillation under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane-ethyl acetate 90:10-75:25) and crystallized from ethyl acetate and hexane to obtain the title compound 1.60 g as a colorless crystal (yield 83%). Melting point was 152 to 155° C.

Workup

  1. additionwas added under ice cooling
  2. stirringthe mixture was stirred for 2 hours
  3. temperatureunder reflux
  4. additionwere serially added
  5. stirringThe mixture was stirred for 1 hour at room temperature
  6. extractionextraction
  7. washThe extract was washed with saturated saline
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customAfter that, the solvent was removed by distillation under reduced pressure
  10. customThe resulting residue was purified by silica gel chromatography (hexane-ethyl acetate 90:10-75:25)
  11. customcrystallized from ethyl acetate and hexane

Sources & evidence

ORD record
ord-0b5a2d331dc64c699a31b7538a8f6a08
Source dataset
uspto-grants-2015_02
Patent number
US08957069B2

Reaction notes

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