Benzyl Bromide → (S)-1-Benzyl-2-methylpiperazine

tert-Butyl (3S)-3-methylpiperazine-1-carboxylate (380.0 g, 1.897 mol) and benzyl bromide (248 mL, 2.09 mol) were mixed in acetonitrile (440 mL). Triethylamine (300.0 mL, 2.152 mol) was carefully added and the mixture was refluxed overnight. After the mixture was cooled down to room temperature, the solid was filtered out. The filtrate was concentrated. The residue was combined with the solid and dissolved in methylene chloride. The methylene chloride solution was washed with 1N NaOH and dried over magnesium sulfate. After the solvent was removed, the residue was directly treated with 6 N HCl at 0° C., and 3 hours later, the solution was basified by slowly adding solid sodium hydroxide. The resulting mixture was extracted with methylene chloride and the extracts were dried over magnesium sulfate. After removal of the solvent, 330 g (91.4%) of product was obtained. The product was used directly for next step. 1H NMR (400 MHz, CDCl3) δ (ppm) 7.30 (m, 5H), 4.05 (d, 1H), 3.15 (d, 1H), 2.92 (m, 1H), 2.83 (m, 2H), 2.67 (m, 1H), 2.60 (m, 1H), 2.38 (m, 1H), 2.36 (bs, 2H), 2.06 (m, 1H), 1.14 (d, 3H). MS (EI) 191.1 (M+1).

1. temperaturethe mixture was refluxed overnight
2. filtrationthe solid was filtered out
3. concentrationThe filtrate was concentrated
4. dissolutiondissolved in methylene chloride
5. washThe methylene chloride solution was washed with 1N NaOH
6. dry with materialdried over magnesium sulfate
7. customAfter the solvent was removed
8. additionthe residue was directly treated with 6 N HCl at 0° C.
9. custom3 hours
10. additionby slowly adding solid sodium hydroxide
11. extractionThe resulting mixture was extracted with methylene chloride
12. dry with materialthe extracts were dried over magnesium sulfate
13. customAfter removal of the solvent

ORD record

ord-464abbbddba24e0bb0d3b68c3d0bac68

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08268826B2