3-Methylbenzylpiperazine → HCID 18955924, compound

HRID 893287Notes

Reaction equation

HRID 893287 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:12]=[CH:13][CH:14]=1)[CH2:5][N:6]1[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1.[CH2:15]([O:22][C:23]1[CH:24]=[C:25]([CH:35]=[CH:36][CH:37]=1)[CH:26](Cl)[C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C1(C)C=CC=CC=1.C(OCC)C>[CH2:15]([O:22][C:23]1[CH:24]=[C:25]([CH:35]=[CH:36][CH:37]=1)[CH:26]([N:9]1[CH2:8][CH2:7][N:6]([CH2:5][C:4]2[CH:12]=[CH:13][CH:14]=[C:2]([CH3:1])[CH:3]=2)[CH2:11][CH2:10]1)[C:27]1[CH:28]=[CH:29][C:30]([Cl:33])=[CH:31][CH:32]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

5

Reactant 2

HCID 792133-MethylbenzylpiperazineHCID 18955928HCID 18955928, compound

Product 1

HCID 18955924HCID 18955924, compoundYield 53%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

The crude piperazine derivative from above (11.0 g, 56 mmole) was dissolved in 150 ml of toluene and added to 19.2 g (56 mmole) of 3-benzyloxy-4'-chlorobenzhydryl chloride (see U.S. Pat. No. 4,757,074) and heated to reflux for 40 hours. The reaction was cooled to room temperature, diluted to 600 ml with diethyl ether, and washed with 100 ml of 1.0 M sodium hydroxide followed by three 200 ml portions of water and 100 ml of saturated sodium chloride. The product was dried over sodium sulfate and the solvent removed to give 27.0 g of crude product as a dark oil. The material was purified by chromatography on silica gel (Waters Prep 500) with 0.1% triethylamine in dichloromethane to give 14.7 g (53%) of 1-(3-benzyloxy-4'-chlorobenzhydryl)-4-(3-methylbenzyl) piperazine as a dark oil. A 5.0 g portion of the oil was dissolved in 00 ml of 2:1 ethanol:methanol and treated with an excess of ethanolic hydrochloric acid to produce the dihydrochloride salt of the product. Addition of 150 ml diethyl ether and cooling provided 1.74 g of the salt as white crystals, mp. 204°-208° C. Calc. for C32H33ClN2O 2HCl: C, 67.43; H, 6.19; N, 4.91; Cl, 18.66. Found: C, 67.15; H, 6.14; N, 4.87; Cl, 18.58.

Workup

  1. temperature4,757,074) and heated
  2. temperatureto reflux for 40 hours
  3. washwashed with 100 ml of 1.0 M sodium hydroxide
  4. dry with materialThe product was dried over sodium sulfate
  5. customthe solvent removed
  6. customto give 27.0 g of crude product as a dark oil
  7. customThe material was purified by chromatography on silica gel (Waters Prep 500) with 0.1% triethylamine in dichloromethane

Sources & evidence

ORD record
ord-e44f66abc49341ccbf4fad32b0c9018b
Source dataset
uspto-grants-1992_06
Patent number
US05124330

Reaction notes

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