1-Methylpiperazine → 4-((4-Methylpiperazin-1-yl)methyl)aniline

HRID 1442652Notes

Reaction equation

HRID 1442652 reaction equation
CN1CCNCC1.[CH3:8][N:9]1[CH2:14][CH2:13][N:12]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[CH:18][CH:17]=2)[CH2:11][CH2:10]1.[BH4-].[Na+]>CO.Cl.O.O.O.O.O.O.[Ni](Cl)Cl>[CH3:8][N:9]1[CH2:14][CH2:13][N:12]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=2)[CH2:11][CH2:10]1

Participants

7

Reactant 3

HCID 531671-MethylpiperazineHCID 6777951-Methyl-4-(4-nitrobenzyl)piperazineHCID 4311764Sodium borohydride

Product 1

HCID 31539964-((4-Methylpiperazin-1-yl)methyl)aniline

Reagents, catalysts & solvents 3

HCID 11791229Dichloronickel;hexahydrateCatalystHCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent

Procedure

Using the procedure of Example 1, 1-methyl-piperazine Compound 46a1 was used in place of Compound 1n2 and carried forward to prepare 1-methyl-4-(4-nitro-benzyl)-piperazine Compound 46a2. Nickel chloride hexahydrate (45.7 g, 192 mmol) was added to a solution of Compound 46a2 (17.9 g, 87.4 mmol) in methanol (250 mL). Twenty portions of sodium borohydride (500 mg each, 264 mmol total) were then added to the reaction mixture over a period of about 2 hr. The mixture was then carefully diluted at 0° C. with concentrated HCl to give a transparent green solution. The mixture was subsequently washed with ethyl ether. The cooled aqueous layer was adjusted to pH 10 with NH4OH (28%) and then extracted with EtOAc. The combined organic layers were dried over MgSO4, then filtered and evaporated in vacuo to give 4-(4-methyl-piperazin-1-ylmethyl)-phenylamine Compound 46a (17.6 g) as a yellow foam. 1H NMR (DMSO-d6) δ 6.91 (d, J=8.2 Hz, 2H); 6.50 (d, J=8.2 Hz, 2H); 4.94 (br s, 2H); 3.28 (s, 2H); 2.44-2.26 (m, 8H); 2.19 (s, 3H).

Workup

  1. customto give a transparent green solution
  2. washThe mixture was subsequently washed with ethyl ether
  3. extractionextracted with EtOAc
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. customevaporated in vacuo

Sources & evidence

ORD record
ord-81c3badf169f4d1580d3e5144aa7865f
Source dataset
uspto-grants-2010_02
Patent number
US07659284B2

Reaction notes

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