反应详情

温度

20 °C

A 100 mL, three-necked round-bottom flask was charged with cis-2,3-dimethylpiperazine (Helvetica Chimica Acta, 1994, 77, 1057-64) (1.781 g, 15.6 mmol). The flask was cooled in an ice bath, and a solution of methanesulfonic acid (2.02 mL, 31.2 mmol) in 1.4 mL of water was added slowly, maintaining the temperature below 40° C. The solution was cooled to 20° C., and 2 mL of ethanol was added. The pH was adjusted to 4 with 60% aqueous potassium acetate, and then benzyl chloroformate (2.08 mL, 14.8 mmol in 1 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 the addition of 6 N NaOH, with cooling to maintain temperature below 40° C. The aqueous solution was extracted with ethyl acetate, and the combined extracts were dried over magnesium sulfate and concentrated in vacuo to provide phenylmethyl cis-2,3-dimethyl-1-piperazinecarboxylate (enantiomeric mixture) as a yellow oil (1.77 g, 46%). 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 the addition of 6 N NaOH
12. temperaturewith cooling
13. temperatureto maintain temperature below 40° C
14. extractionThe aqueous solution was extracted with ethyl acetate
15. dry with materialthe combined extracts were dried over magnesium sulfate
16. concentrationconcentrated in vacuo