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

Participants

Reaction Steps

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).

Provenance & Evidence