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

HRID 1272306Notes

Reaction equation

HRID 1272306 reaction equation
CS(Cl)(=O)=O.[CH3:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][N:17]([C:20]3[C:21]([CH3:34])=[C:22]([CH3:33])[C:23]4[O:27][C:26]([CH3:29])([CH3:28])[CH:25](O)[C:24]=4[C:31]=3[CH3:32])[CH2:16][CH2:15]2)=[CH:10][CH:9]=1.C(N(CC)CC)C.[CH2:42]([NH2:49])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.C(=O)([O-])[O-].[K+].[K+]>C1COCC1.CCCCCC.C(OCC)(=O)C>[CH2:42]([NH:49][CH:25]1[C:24]2[C:31]([CH3:32])=[C:20]([N:17]3[CH2:16][CH2:15][N:14]([C:11]4[CH:12]=[CH:13][C:8]([O:7][CH3:6])=[CH:9][CH:10]=4)[CH2:19][CH2:18]3)[C:21]([CH3:34])=[C:22]([CH3:33])[C:23]=2[O:27][C:26]1([CH3:29])[CH3:28])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1

Participants

8

Reactant 5

HCID 7504BenzylamineHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 674202085-(4-(4-Methoxyphenyl)piperazin-1-yl)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-ol

Product 1

HCID 10206391N-benzyl-5-(4-(4-methoxyphenyl)piperazin-1-yl)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-amineYield 76.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

Methane sulfonyl chloride (0.12 mL, 1.55 mmol) was added dropwise to a solution of 5-(4-(4-methoxyphenyl)piperazin-1-yl)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-3-ol (300 mg, 0.757 mmol) obtained in Reference Example 18 and triethylamine (0.4 mL, 2.87 mmol) in THF (3 ml) under ice cooling. The reaction mixture was stirred for 10 minutes and then benzylamine (0.4 mL, 3.66 mmol) was added. The resulting mixture was stirred under ice cooling for 1 hour. The reaction mixture was poured into 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 silica gel column chromatography (hexane then hexane/ethyl acetate=5/1) to obtain 280 mg (yield 76%) of the title compound via recrystallization (ethanol). mp. 93–95° C.

Workup

  1. stirringThe resulting mixture was stirred under ice cooling for 1 hour
  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

Sources & evidence

ORD record
ord-2cb814718cd74cfbb0437efe3303633d
Source dataset
uspto-grants-2007_04
Patent number
US07208495B2

Reaction notes

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