1-(2-Bromophenyl)piperazine → 1-(2-Bromophenyl)-4-methylpiperazine

HRID 1777745Notes

Reaction equation

HRID 1777745 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1.[BH3-][C:15]#N.[Na+]>C=O>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:13][CH2:12][N:11]([CH3:15])[CH2:10][CH2:9]1

Participants

4

Reactant 2

HCID 27571531-(2-Bromophenyl)piperazineHCID 5003444Sodium cyanoborohydride2×

Product 1

HCID 120694321-(2-Bromophenyl)-4-methylpiperazineYield 52.4%

Reagents, catalysts & solvents 1

HCID 712FormaldehydeSolvent

Procedure

1-(2-Bromophenyl)piperazine (200 mg) was dissolved in formaldehyde (36.5% in water, 0.603 mL) and the solution was stirred 3 h at RT. NaBH3CN (78.2 mg) was added and the mixture was stirred at RT overnight. NaBH3CN (78.2 mg) was added again and the mixture was stirred at RT for 6 h. The solvents were removed in vacuo and the residue was taken up in EA, washed with sat. NaHCO3, dried (Na2SO4) and evaporated to dryness. The residue was purified by CC (Biotage, SNAP 25 g cartridge, solvent A: Hept; solvent B: EA; gradient in % B: 18 for 4CV, 18 to 100 over 10CV, 100 for 2CV, then MeOH flush for 4CV) to afford 1-(2-bromophenyl)-4-methylpiperazine (111 mg, colorless oil). LC-MS (B): tR=0.57 min; [M+H]+: 255.05.

Workup

  1. stirringthe mixture was stirred at RT overnight
  2. stirringthe mixture was stirred at RT for 6 h
  3. customThe solvents were removed in vacuo
  4. washwashed with sat. NaHCO3
  5. dry with materialdried (Na2SO4)
  6. customevaporated to dryness
  7. customThe residue was purified by CC (Biotage, SNAP 25 g cartridge, solvent A
  8. customgradient in % B: 18 for 4CV, 18 to 100 over 10CV, 100 for 2CV, then MeOH flush for 4CV)

Sources & evidence

ORD record
ord-45ab6736a9e845f6a29f747c5214735c
Source dataset
uspto-grants-2016_02
Patent number
US09266876B2

Reaction notes

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