Triethylamine → (2R)-4-benzyl-1-[3,5-bis(trifluoro-methyl)benzoyl]-2-(1H-indol-3-yl-methyl)piperazine

HRID 1379187Notes

Reaction equation

HRID 1379187 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=1)[C:6]([OH:8])=O.[CH2:18]([N:25]1[CH2:30][CH2:29][NH:28][C@H:27]([CH2:31][C:32]2[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[NH:34][CH:33]=2)[CH2:26]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(N(CC)CC)C.[I-].ClC1C=CC=C[N+]=1C>ClCCl.O>[CH2:18]([N:25]1[CH2:30][CH2:29][N:28]([C:6](=[O:8])[C:5]2[CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=[C:3]([C:2]([F:1])([F:17])[F:16])[CH:4]=2)[C@H:27]([CH2:31][C:32]2[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[NH:34][CH:33]=2)[CH2:26]1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 128893,5-Bis(trifluoromethyl)benzoic acidHCID 1670692-Chloro-1-methylpyridinium iodideHCID 53910379(3R)-1-benzyl-3-(1H-indol-3-yl-methyl)piperazine

Product 1

HCID 54406912(2R)-4-benzyl-1-[3,5-bis(trifluoro-methyl)benzoyl]-2-(1H-indol-3-yl-methyl)piperazineYield 35.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 3,5-bis(trifluoromethyl)benzoic acid (1.15 g) and (3R)-1-benzyl-3-(1H-indol-3-yl-methyl)piperazine (1.61 g) in dichloromethane (80 ml) was added triethylamine (1.55 ml) at room temperature under nitrogen atmosphere. 2-Chloro-1-methylpyridinium iodide (1.37 g) was added, and the mixture was stirred at room temperature for 2.5 hours. The resulting mixture was poured into water (20 ml). The organic layer was washed successively with 0.5N hydrochloric acid, water, aqueous sodium bicarbonate solution and brine, and dried over magnesium sulfate. After evaporation under reduced pressure, the residue was chromatographed on silica gel with toluene - ethyl acetate (4:1) as an eluent to give (2R)-4-benzyl-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-yl-methyl)piperazine (0.87 g) as a syrup.

Workup

  1. washThe organic layer was washed successively with 0.5N hydrochloric acid, water, aqueous sodium bicarbonate solution and brine
  2. dry with materialdried over magnesium sulfate
  3. customAfter evaporation under reduced pressure
  4. customthe residue was chromatographed on silica gel with toluene - ethyl acetate (4:1) as an eluent

Sources & evidence

ORD record
ord-a50541bd47f74b1d8b7896e499ebe8fe
Source dataset
uspto-grants-1997_09
Patent number
US05670505

Reaction notes

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