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

HRID 1272292Notes

Reaction equation

HRID 1272292 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=1.[CH3:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]2[CH2:27][CH2:26][N:25]([C:28]3[C:29]([CH3:42])=[C:30]([CH3:41])[C:31]4[O:35][C:34]([CH3:37])([CH3:36])[C:33](=[O:38])[C:32]=4[C:39]=3[CH3:40])[CH2:24][CH2:23]2)=[CH:18][CH:17]=1.O>C1COCC1>[OH:38][C:33]1([C:7]2[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=2)[C:32]2[C:39]([CH3:40])=[C:28]([N:25]3[CH2:24][CH2:23][N:22]([C:19]4[CH:18]=[CH:17][C:16]([O:15][CH3:14])=[CH:21][CH:20]=4)[CH2:27][CH2:26]3)[C:29]([CH3:42])=[C:30]([CH3:41])[C:31]=2[O:35][C:34]1([CH3:37])[CH3:36]

Participants

6

Reactant 4

HCID 962WaterHCID 78054-BromotolueneHCID 229355955-[4-(4-methoxyphenyl)piperazin-1-yl]-2,2,4,6,7-pentamethyl-1-benzofuran-3(2H)-oneHCID 178418339Butyllithium

Product 1

HCID 102778831-(3-Hydroxy-2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl)-4-(4-methoxyphenyl)piperazineYield 91.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

n-Butyllithium (hexane solution 1.50 M, 3.40 mL, 5.10 mmol) was added dropwise to solution of 4-bromotoluene (1.10 g, 6.43 mmol) in THF (10 ml) under a stream of argon at −70° C. or less and the mixture was stirred for 30 minutes. To the mixture was added dropwise a solution of 4-(4-methoxyphenyl)-1-(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-on-5-yl)piperazine (1.00 g, 2.5 mmol) obtained in Reference Example 13 in THF (3 ml) at −70° C. or less and the mixture was allowed to warm to 0° C. After stirring under ice cooling for 30 minutes, 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 under reduced pressure. The residue was purified with silica gel column chromatography (hexane/ethyl acetate=5/1) to obtain 1.11 g (yield 90%) of the title compound via recrystallization (ethyl acetate-hexane). mp. 145–147° C.

Workup

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

Sources & evidence

ORD record
ord-4856cdaac2a749318d961888c14361f6
Source dataset
uspto-grants-2007_04
Patent number
US07208495B2

Reaction notes

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