Phenol → HCID 6918291, compound

HRID 1940213Notes

Reaction equation

HRID 1940213 reaction equation
Br[CH2:2][CH:3]1[C:7]2[C:8]([CH3:15])=[C:9]([OH:14])[C:10]([CH3:13])=[C:11]([CH3:12])[C:6]=2[O:5][C:4]1([CH3:17])[CH3:16].C1(O)C=CC=CC=1.[CH3:25][N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1>C(#N)C>[CH3:16][C:4]1([CH3:17])[CH:3]([CH2:2][N:29]2[CH2:30][CH2:31][N:26]([CH3:25])[CH2:27][CH2:28]2)[C:7]2[C:8]([CH3:15])=[C:9]([OH:14])[C:10]([CH3:13])=[C:11]([CH3:12])[C:6]=2[O:5]1

Participants

5

Reactant 3

HCID 996PhenolHCID 531671-MethylpiperazineHCID 10334891HCID 10334891, compound

Product 1

HCID 6918291HCID 6918291, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 3-bromomethyl-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-ol (81 g, 270 mmol), phenol (26.75 g, 284 mmol) and N-methylpiperazine (28.47 g, 284 mmol) in acetonitrile (300 ml) is stirred at reflux temperature for 60 hrs. The precipitate that formed is collected, washed with acetonitrile and slurtied in 10% sodium bicarbonate solution. The product is extracted twice with ethyl acetate, and the extract is washed with water and brine, dried (sodium sulfate) and evaporated. The resulting solid is dissolved in ethanol (150 mL) and 2N hydrochloric acid (150 mL), and evaporated to near dryness. The resulting solid is recrystallized in ethanol/ethyl acetate to give after drying at 60° C. under 13 Pa and equilibration in a moist atmosphere for 24 hrs, 48.60 g (44%) of 2,2,4,6,7-pentamethyl-3-[(4-methylpiperazino)-methyl]-2,3-dihydro-1-benzofuran-5-ol dihydrochloride hydrate, mp=172°-3° C.(dec.). A second crop of 19.63 g of 2,2,4,6,7-pentamethyl-3-[(4-methylpiperazino)-methyl]-2,3-dihydro-1-benzofuran-5-ol (total yield 63%) could be obtained from the filtrate after purification of the free base by column chromatography on silica gel eluting with dichloromethane/methanol 9:1.

Workup

  1. temperatureat reflux temperature for 60 hrs
  2. customThe precipitate that formed
  3. customis collected
  4. washwashed with acetonitrile
  5. extractionThe product is extracted twice with ethyl acetate
  6. washthe extract is washed with water and brine
  7. dry with materialdried (sodium sulfate)
  8. customevaporated
  9. dissolutionThe resulting solid is dissolved in ethanol (150 mL)
  10. custom2N hydrochloric acid (150 mL), and evaporated
  11. customThe resulting solid is recrystallized in ethanol/ethyl acetate
  12. customto give
  13. customafter drying at 60° C. under 13 Pa and equilibration in a moist atmosphere for 24 hrs

Sources & evidence

ORD record
ord-11bc0edce4c94e979569e4017c76b9f0
Source dataset
uspto-grants-1997_12
Patent number
US05698696

Reaction notes

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