反应详情

A solution of N-Benzyl-4-Acetyl-4-(4-Chlorobenzyl)-piperidine (600 mg, 1.75 mmol) and dimethyl oxalate (310 mg, 2.63 mmol) in dimethoxyethane (20 mL) was treated with sodium hydride (105 mg of a 60% dispersion in mineral oil, 2.63 mmol) and heated to reflux for 3 hours. The reaction was then cooled to room temperature, poured into 1 N aqueous HCl (200 mL) and extracted with ethyl ether (1×50 mL). The ether extract was discarded. The pH of the aqueous phase was adjusted to pH 8 and extracted with ethyl acetate (3×200 mL). The combined extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated at reduced pressure. The crude ester thus obtained was dissolved in THF (5 mL) and 3 N HCl (20 mL) and heated to reflux for 1 hour. The reaction was then cooled to room temperature, and concentrated at reduced pressure. The residue was triturated with tetrahydrofuran and the solid collected by filtration and crystallized from isopropanol to give 200 mg of the title compound. mp. 189°-181° C.

1. temperatureheated
2. temperatureto reflux for 3 hours
3. extractionextracted with ethyl ether (1×50 mL)
4. extractionThe ether extract
5. extractionextracted with ethyl acetate (3×200 mL)
6. dry with materialThe combined extracts were dried over anhydrous magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated at reduced pressure
9. customThe crude ester thus obtained
10. temperatureto reflux for 1 hour
11. temperatureThe reaction was then cooled to room temperature
12. concentrationconcentrated at reduced pressure
13. customThe residue was triturated with tetrahydrofuran
14. filtrationthe solid collected by filtration
15. customcrystallized from isopropanol