反应详情

温度

5 °C

Add oxalyl chloride (5.08 mL, 0.058 mol) dropwise to a suspension of 1-methyl-4-carboxypiperidine HCl (10 g, 0.056 mol) in THF (100 mL) in the presence of a catalytic amount of DMF (0.1 mL) at room temperature. Stir for 1 hr. and then heat the mixture at reflux until gas emission stops (about 1 hr.). Cool the white suspension to 5° C. and add a solution of pyrrolidine (7.92 g, 0.111 mol) and triethylamine (16.9 g, 0.167 mol) dropwise over 30 min at a temperature between 5 and 13° C. Stir the suspension for 30 min. at 10° C. and then warm to room temperature. Quench the reaction mixture by adding 30% NaOH (20 mL, 0.2 mol) and water (10 mL). Decant the aqueous layer and extract with THF (200 mL). Combine the organic layers, dry over Na2CO3, and evaporate under vacuum at 40° C. Solubilize the resulting oil in cyclohexane (200 mL). Evaporate under reduced pressure at 40° C. to give a white solid (11 g). Heat the white solid (11 g) under reflux in cyclohexane (50 mL) untill completely dissolved. Cool the solution to room temperature and stir at room temperature for 2 hr. Filter the suspension wash the crystals with cyclohexane (10 mL). Dry the white crystals under reduced pressure at 40° C. to provide the title intermediate (7.76 g, 75% yield).

1. temperatureand then heat the mixture
2. temperatureat reflux until gas emission
3. custom(about 1 hr.)
4. stirringStir the suspension for 30 min. at 10° C.
5. temperaturewarm to room temperature
6. customQuench the reaction mixture
7. customDecant the aqueous layer
8. extractionextract with THF (200 mL)
9. dry with materialCombine the organic layers, dry over Na2CO3
10. customevaporate under vacuum at 40° C
11. customEvaporate under reduced pressure at 40° C.