反应详情

温度

20 °C

A 100 mL, three-necked round-bottom flask was charged with a mixture of trans-2,3-dimethylpiperazine and cis-2,3-dimethylpiperazine (Yakugaku Zasshi, 1958, 78, 229-232) (3.571 g, 31.1 mmol). The flask was cooled in an ice bath, and a solution of methanesulfonic acid (3.95 mL, 60.9 mmol) in 2.7 mL of water was added slowly, maintaining the temperature below 40° C. The solution was cooled to 20° C., and 4 mL of ethanol was added. The pH was adjusted to 4 with 60% aqueous potassium acetate, and then benzyl chloroformate (3.86 mL, 27.4 mol in 2 mL of THF) and potassium acetate solutions were simultaneously added dropwise with adjustment of the rate to maintain the reaction solution at pH 4, with cooling to maintain the temperature at 25° C. After the mixture was stirred an additional hour, the organic solvents were removed, and the remaining aqueous solution was washed with ethyl acetate. The ethyl acetate wash was extracted with 1 M HCl twice to recover the desired product. The acid extracts were combined with the original aqueous solution, and the pH was adjusted to 11 by addition of 6 N NaOH, with cooling to maintain the temperature below 40° C. The aqueous solution was then extracted with ethyl acetate, and the ethyl acetate extraction was dried over magnesium sulfate. Filtration and removal of the solvent provided all four stereoisomers of phenylmethyl 2,3-dimethyl-1-piperazinecarboxylate as a dark brown oil (3.11 g, 41%). LCMS: (M+H)+: 249.1.

1. temperatureThe flask was cooled in an ice bath
2. temperaturemaintaining the temperature below 40° C
3. temperatureto maintain the reaction solution at pH 4
4. temperaturewith cooling
5. temperatureto maintain the temperature at 25° C
6. customthe organic solvents were removed
7. washthe remaining aqueous solution was washed with ethyl acetate
8. washThe ethyl acetate wash
9. extractionwas extracted with 1 M HCl twice
10. customto recover the desired product
11. additionthe pH was adjusted to 11 by addition of 6 N NaOH
12. temperaturewith cooling
13. temperatureto maintain the temperature below 40° C
14. extractionThe aqueous solution was then extracted with ethyl acetate
15. extractionthe ethyl acetate extraction
16. dry with materialwas dried over magnesium sulfate
17. filtrationFiltration and removal of the solvent