Hydrochloric Acid → 1-Benzyl-3,3-dimethylpiperidin-4-one

Temperature

-6.5 °C

1-Benzyl-4-piperidone (100 gm, 0.53 mol) diluted with 100 ml THF was added to a suspension of 60% NaH (42 g, 1.05 mol) in 700 ml THF at −10 to −5° C. The mixture was stirred for 1 hour and methyl iodide (150 gm, 1.06 mol) diluted in 50 ml THF was added, maintaining the temperature between −3 to −10° C. The resultant mixture was stirred. Ethyl acetate (800 ml) was added to the reaction mixture followed addition of 300 ml water. The organic layer was separated washed with 2×300 ml water and concentrated under vacuum to obtain a syrup. The syrup was triturated with 200 ml hexane. the mass was filtered at room temperature over celite and the filtrate concentrated to afford a 121 gm of crude compound. The crude compound upon high vacuum distillation afforded 85 g distillate. To the distillate (50 gm) was charged 50 ml of concentrated hydrochloric acid. The suspension was stirred for 15 minutes and hydrochloric acid was evaporated under vacuum to obtain a thick residue. Isopropanol (50 ml) was added to this residue and was evaporated under vacuum to obtain a solid. The solid was dissolved in 200 ml isopropanol under reflux and stirring, and cooled under stirring to effect crystallization. The crystalline solid was filtered under suction at 20-30° C. to give a white crystalline compound as hydrochloride salt of 1-benzyl-3,3-dimethyl-4-piperidone. The solid was dissolved in 100 ml water and made alkaline with aqueous ammonia solution to pH 10-11. Alkaline aqueous phase was extracted with 50 ml chloroform thrice. Combined organic extract was washed with water, dried over sodium sulfate and then evaporated under vacuum to afford 28 g (80%) compound as an oil.

1. additionwas added
2. customThe organic layer was separated
3. washwashed with 2×300 ml water
4. concentrationconcentrated under vacuum
5. customto obtain a syrup
6. customThe syrup was triturated with 200 ml hexane
7. filtrationthe mass was filtered at room temperature over celite
8. concentrationthe filtrate concentrated
9. customto afford a 121 gm of crude compound
10. distillationThe crude compound upon high vacuum distillation
11. customafforded 85 g distillate
12. stirringThe suspension was stirred for 15 minutes
13. customhydrochloric acid was evaporated under vacuum
14. customto obtain a thick residue
15. customwas evaporated under vacuum
16. customto obtain a solid
17. temperatureunder reflux
18. stirringstirring
19. temperaturecooled
20. stirringunder stirring
21. customcrystallization
22. filtrationThe crystalline solid was filtered under suction at 20-30° C.

ORD record

ord-0b18b86c03a64eea90dfa404f6e2f55c

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07393957B2