Benzylethanolamine → 2-Carbamoyl-4-(2-methylphenyl)piperazine

HRID 1740579Notes

Reaction equation

HRID 1740579 reaction equation
C(NCCO)C1C=CC=CC=1.Cl.ClCCNCC1C=CC=CC=1.S(Cl)(Cl)=O.Cl.C(NCCNC1C=CC=CC=1C)C1C=CC=CC=1.NC1C(C)=CC=CC=1.BrC(CBr)C(N)=O.[CH2:62]([N:69]1[CH2:74][CH2:73][N:72]([C:75]2[CH:80]=[CH:79][CH:78]=[CH:77][C:76]=2[CH3:81])[CH2:71][CH:70]1[C:82](=[O:84])[NH2:83])[C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1.[H][H]>C(Cl)Cl.CO.C(O)C.[OH-].[OH-].[Pd+2]>[CH2:62]([N:69]1[CH2:74][CH2:73][N:72]([C:75]2[CH:80]=[CH:79][CH:78]=[CH:77][C:76]=2[CH3:81])[CH2:71][CH:70]1[C:82](=[O:84])[NH2:83])[C:63]1[CH:64]=[CH:65][CH:66]=[CH:67][CH:68]=1.[C:82]([CH:70]1[CH2:71][N:72]([C:75]2[CH:80]=[CH:79][CH:78]=[CH:77][C:76]=2[CH3:81])[CH2:73][CH2:74][NH:69]1)(=[O:84])[NH2:83]

Participants

14

Reactant 8

HCID 4348BenzylethanolamineHCID 7242O-ToluidineHCID 24386Thionyl ChlorideHCID 857982,3-DibromopropionamideHCID 13054189Benzenemethanamine, N-(2-chloroethyl)-, hydrochloride (1:1)2×HCID 218372261-Benzyl-4-(2-methylphenyl)piperazine-2-carboxamideHCID 21837245N-benzyl-N'-(2-methylphenyl)-1,2-diaminoethane hydrochloride2×HCID 178418361HCID 178418361, compound

Product 2

HCID 154305682-Carbamoyl-4-(2-methylphenyl)piperazineHCID 218372261-Benzyl-4-(2-methylphenyl)piperazine-2-carboxamide

Reagents, catalysts & solvents 4

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolventHCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

2-Benzylaminoethanol (20 g, 0.13 mol) was converted to N-(2-chloroethyl)-N-benzylamine hydrochloride with thionyl chloride (31 g, 0.26 mol) according to the procedure described in J. Chem. Soc. 1955, p. 896. N-(2-chloroethyl)-N-benzylamine hydrochloride (4.0 g, 19 mmol) was converted to N-benzyl-N'-(2-methylphenyl)-1,2-diaminoethane hydrochloride by the procedure of Syn. Comm., 1988, vol. 18, p. 45-50, using o-toluidine (6.1 g, 57 mmol) in place of aniline. 1-Benzyl-2-carbamoyl-4-(2-methylphenyl)-piperazine was prepared from 2,3-dibromopropionamide (7.9 g, 34 mmol) by the procedure of J. Med. Chem., 1992, vol. 35, p. 743-750 using N-benzyl-N'-(2-methylphenyl)-1,2-diaminoethane hydrochloride (4.95 g, 18 mmol) in place of N-benzyl-N'-phenyl-1,2-diaminoethane hydrochloride (TLC: Rf=0.51 (5% methanol in methylene chloride; FABMS: M+H @ m/e=310). 1-Benzyl-2-carbamoyl-4-(2-methyl-phenyl)piperazine (2.64 g, 8.53 mmol) and palladium hydroxide/carbon (430 mg) were combined in a mixture of methanol (35 ml) and ethanol (35 ml) and shaken in an atmosphere of hydrogen at 55 psi for 6 hours at ambient temperature. The mixture was filtered and the filtrate was concentrated in vacuo. The residue was reconcentrated in vacuo from ether three times to provide 2-carbamoyl-4-(2-methylphenyl)piperazine as a solid.

Workup

  1. filtrationThe mixture was filtered
  2. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-d8f56a060ba14e548e24716c3889848b
Source dataset
uspto-grants-1999_10
Patent number
US05968938

Reaction notes

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