Aniline → N-phenyl-5-(4-(4-methoxyphenyl)piperazin-1-yl)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-amine

HRID 1272307Notes

Reaction equation

HRID 1272307 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([N:28]2[CH2:33][CH2:32][N:31]([C:34]3[C:35]([CH3:48])=[C:36]([CH3:47])[C:37]4[O:41][C:40]([CH3:43])([CH3:42])[CH:39](O)[C:38]=4[C:45]=3[CH3:46])[CH2:30][CH2:29]2)=[CH:24][CH:23]=1.CCCCCC.C(OCC)(=O)C>CO>[C:2]1([NH:1][CH:39]2[C:38]3[C:45]([CH3:46])=[C:34]([N:31]4[CH2:30][CH2:29][N:28]([C:25]5[CH:24]=[CH:23][C:22]([O:21][CH3:20])=[CH:27][CH:26]=5)[CH2:33][CH2:32]4)[C:35]([CH3:48])=[C:36]([CH3:47])[C:37]=3[O:41][C:40]2([CH3:43])[CH3:42])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6115AnilineHCID 521998p-Toluenesulfonic acid monohydrateHCID 21226206Ethyl acetate hexaneHCID 674202085-(4-(4-Methoxyphenyl)piperazin-1-yl)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-ol

Product 1

HCID 10298980N-phenyl-5-(4-(4-methoxyphenyl)piperazin-1-yl)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-amineYield 87.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

Aniline (120 mg, 1.29 mmol) and p-toluenesulfonic acid monohydrate (25.0 mg, 0.131 mmol) were 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 (260 mg, 0.656 mmol) obtained in Reference Example 18 in methanol (3 ml) and the mixture was stirred at 60° C. for 120 hours. The resulting mixture was concentrated under reduced pressure. The residue was made to basic with 1N aqueous potassium carbonate 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 basic column chromatography (hexane then hexane/ethyl acetate=25/1) to obtain 270 mg (yield 87%) of the title compound via recrystallization (methanol). mp. 90–94° C.

Workup

  1. concentrationThe resulting mixture was concentrated under reduced pressure
  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 basic column chromatography (hexane

Sources & evidence

ORD record
ord-75924681f1624c278172766aa01fef5c
Source dataset
uspto-grants-2007_04
Patent number
US07208495B2

Reaction notes

Loading…