反应详情

温度

-10 °C

To a solution of piperidine-1,2-dicarboxylic acid 1-tert-butyl ester (3.0 g in a mixture of 26 mL dry tetrahydrofuran and 26 mL dry diethyl ether) at -10° C. was added 1.91 mL of triethylamine followed by the dropwise addition of 1.78 mL isobutyl chloroformate. The reaction was stirred at -10° C. for 30 minutes then warmed to 0° C. Over the next hour, 26 mL of a solution of diazomethane in diethyl ether was added (prepared from: 8.0 g Diazald® in 70 mL diethyl ether; 4 g potassium hydroxide; 20 mL 2-(2-ethoxyethoxy)ethanol; 6 mL water and 12 mL diethyl ether using a mini Diazald Kit) and the mixture allowed to stir at room temperature for an additional 2 hours. At this time the reaction was quenched by the addition of 3 mL acetic acid at 0° C. This was then diluted with 100 mL water and 100 mL diethyl ether, the layers separated and the aqueous portion extracted with (2×75 mL) diethyl ether. The combined organics were washed with water (75 mL), saturated sodium bicarbonate (2×75 mL) and brine (75 mL) then dried over magnesium sulfate. Removal of the solvent in vacuo and purification of the residue by flash chromatography on silica gel (hexane:ethyl acetate, 8:2) gave the title compound (2.99 g).

1. temperaturethen warmed to 0° C
2. stirringto stir at room temperature for an additional 2 hours
3. customAt this time the reaction was quenched by the addition of 3 mL acetic acid at 0° C
4. additionThis was then diluted with 100 mL water and 100 mL diethyl ether
5. customthe layers separated
6. extractionthe aqueous portion extracted with (2×75 mL) diethyl ether
7. washThe combined organics were washed with water (75 mL), saturated sodium bicarbonate (2×75 mL) and brine (75 mL)
8. dry with materialthen dried over magnesium sulfate
9. customRemoval of the solvent
10. customin vacuo and purification of the residue by flash chromatography on silica gel (hexane:ethyl acetate, 8:2)