Water → 1-(3-(Benzyloxy)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)-4-(4-methoxyphenyl)piperazine

HRID 1272322Notes

Reaction equation

HRID 1272322 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[C:18]([CH3:31])=[C:19]([CH3:30])[C:20]4[O:24][C:23]([CH3:26])([CH3:25])[CH:22]([OH:27])[C:21]=4[C:28]=3[CH3:29])[CH2:13][CH2:12]2)=[CH:7][CH:6]=1.[CH2:32](Br)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.O>CN(C=O)C>[CH2:32]([O:27][CH:22]1[C:21]2[C:28]([CH3:29])=[C:17]([N:14]3[CH2:13][CH2:12][N:11]([C:8]4[CH:7]=[CH:6][C:5]([O:4][CH3:3])=[CH:10][CH:9]=4)[CH2:16][CH2:15]3)[C:18]([CH3:31])=[C:19]([CH3:30])[C:20]=2[O:24][C:23]1([CH3:26])[CH3:25])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 674202085-(4-(4-Methoxyphenyl)piperazin-1-yl)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-ol

Product 1

HCID 184560331-(3-(Benzyloxy)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)-4-(4-methoxyphenyl)piperazineYield 63%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60%, 0.06 g, 1.5 mmol) was added to a solution of 5-(4-(4-methoxyphenyl)piperazin-1-yl)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-ol (0.30 g, 0.75 mmol) obtained in Reference Example 18 in DMF (5 ml) under ice cooling. The mixture was stirred for 30 minutes, and then benzyl bromide (0.14 g, 0.84 mmol) was added. After stirring for 30 minutes under ice cooling, the mixture was stirred for 30 minutes at room temperature. The resulting mixture was poured into water and extracted with ethyl acetate. The organic extract was washed with water and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and concentrated. The residue was purified with silica gel column chromatography (hexane/ethyl acetate=9/1) to obtain 0.23 g (yield 62%) of the title compound via recrystallization (diisopropyl ether-methanol). mp. 98–99° C.

Workup

  1. stirringAfter stirring for 30 minutes under ice cooling
  2. stirringthe mixture was stirred for 30 minutes at room temperature
  3. extractionextracted with ethyl acetate
  4. extractionThe organic extract
  5. washwas washed with water and saturated aqueous sodium chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified with silica gel column chromatography (hexane/ethyl acetate=9/1)

Sources & evidence

ORD record
ord-8326d695d04a426392298a56f831323c
Source dataset
uspto-grants-2007_04
Patent number
US07208495B2

Reaction notes

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