4-氨基哌啶异丙酯

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 14.23 g Freshly distilled 4-(isopropylamino)piperidine (100 mmole, fw=142.25), 28.43 g diisopropylethylamine (DIPEA, 220 mmole, fw=129.25) and 75 mL acetonitrile are placed in a 200 mL heavy-walled, glass pressure vessel that is equipped with a magnetic stirring-bar, thermocouple and pressure head with relief valve. 35.96 g ethyl bromide (330 mmole, fw=108.97) is added to the stirring mixture and pressure vessel is sealed. Initially there is a mild exotherm. The reaction mixture is heated and stirred at 40° C. for 24 hours, and then it is cooled to room temperature. During cooling, white crystals of DIPEA hydrobromide begin to form. The reaction vessel is vented in a hood, and then the reaction mixture is filtered through sintered-glass to remove the unwanted solid. The solvent is removed on a rotary evaporator, and then just enough 50% aqueous NaOH is added (˜28 g) until the mixture is strongly basic. The liquid (acetonitrile, water, DIEPA) is removed using a rotary evaporator and then a vacuum pump (0.5 torr). The residue is twice extracted with 100 mL hot acetonitrile, and the liquids are combined. Anhydrous magnesium sulfate (˜15 g) is added, the liquid is filtered and then placed on a rotary evaporator to remove most of the solvent. Small amounts of acetonitrile are added back to ensure a homogeneous solution, and then peroxide-free diethylether is added to induce crystallization. The mixture is allowed to stand at room temperature for about 4 hours and then at 4° C. overnight. The cold acetonitrile/ether mixture is filtered through sintered glass, washed with ether and then dried by passing dry N2 through the filter. The off-white solid is dried in a vacuum oven overnight yielding 22.1 g (72%) of a sticky, white crystalline solid with purity (HPLC) of about 97%. Recrystallization from acetonitrile/isopropanol/ether mixtures yields a purified product (˜99%). This reaction illustrates a method to carry out multiple alkylations of primary and secondary amines in the presence of a strong, soluble, nonreactive base. Despite the excess alkylating agent, there was no evidence (HPLC) of the tetraalkylated impurity in the reaction mixture or in the final trialkylated product. glass pressure vessel that is equipped with a magnetic stirring-bar is sealed The reaction mixture is heated it is cooled to room temperature During cooling to form the reaction mixture is filtered through sintered-glass to remove the unwanted solid The solvent is removed on a rotary evaporator just enough 50% aqueous NaOH is added (˜28 g) until the mixture The liquid (acetonitrile, water, DIEPA) is removed a rotary evaporator The residue is twice extracted with 100 mL hot acetonitrile Anhydrous magnesium sulfate (˜15 g) is added the liquid is filtered placed on a rotary evaporator to remove most of the solvent Small amounts of acetonitrile are added back peroxide-free diethylether is added crystallization to stand at room temperature for about 4 hours at 4° C. overnight The cold acetonitrile/ether mixture is filtered through sintered glass washed with ether dried The off-white solid is dried in a vacuum oven overnight yielding 22.1 g (72%) of a sticky, white crystalline solid with purity (HPLC) of about 97% Recrystallization from acetonitrile/isopropanol/ether