1-Methylpiperazine → 2-Methyl-4-((4-methylpiperazin-1-yl)methyl)phenol

HRID 1035173Notes

Reaction equation

HRID 1035173 reaction equation
[OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][C:3]=1[CH3:10].[CH3:11][N:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClC(Cl)C>[CH3:10][C:3]1[CH:4]=[C:5]([CH2:6][N:15]2[CH2:16][CH2:17][N:12]([CH3:11])[CH2:13][CH2:14]2)[CH:8]=[CH:9][C:2]=1[OH:1]

Participants

6

Reactant 4

HCID 531671-Methylpiperazine2×HCID 1399014-Hydroxy-3-methylbenzaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 580431092-Methyl-4-((4-methylpiperazin-1-yl)methyl)phenolYield 66.2%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A mixture of 4-hydroxy-3-methylbenzaldehyde (3.27 g, 24 mmol) and 1-methylpiperazine (2.7 g, 27.0 mmol) in dichloroethane (100 mL) was stirred at rt for 30 min. Sodium triacetoxyborohydride (6.2 g, 29 mmol) was added in portions and the reaction mixture was stirred at rt over night. A further portion of 1-methylpiperazine was added and stirring was continued for 24 h. Aqueous NaHCO3 (sat.) was added, the phases were separated and the aqueous phase was saturated with sodium chloride and extracted with DCM twice. The combined organic solutions were dried (MgSO4) and evaporated and the residue was purified by column chromatography on SiO2 using 0-20% MeOH in EtOAc:MeOH 95:5 as eluent. There was obtained 3.50 g (66%) of 9A as a solid. 1H NMR (500 MHz, CDCl3): δ 2.21 (2, 3H), 2.29 (s, 3H), 2.32-2.72 (bm, 8H), 3.42 (s, 2H), 6.55 (d, 1H), 6.90 (d, 1H), 7.02 (s, 1H).

Workup

  1. stirringthe reaction mixture was stirred at rt over night
  2. stirringstirring
  3. waitwas continued for 24 h
  4. customthe phases were separated
  5. extractionextracted with DCM twice
  6. dry with materialThe combined organic solutions were dried (MgSO4)
  7. customevaporated
  8. customthe residue was purified by column chromatography on SiO2 using 0-20% MeOH in EtOAc:MeOH 95:5 as eluent

Sources & evidence

ORD record
ord-ac707b7ff65149f1a1c2b1bc286fe8de
Source dataset
uspto-grants-2013_10
Patent number
US08546375B2

Reaction notes

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