Phenyl piperidyl ketone

Perhydro-imidazo[l,5-fl]pyridines of type 109 are obtained from -p-chlorophenyl-2-piperidyl ketone (108) and phenyl isocyanate. The 3-thioxo analogues (110) are prepared using phenyl isothiocyanate (70USP3494926). 

The manufacture of the cyclohexyl analog is as follows. Phenyl magnesium bromide was prepared from 48.5 g (0.308 mol) of bromobenzene, 7 g (0,29 mol) of magnesium, and 125 ml of dry ether. To it was added at 5°C over a period of A hour 40 g (0.18 mol) of cyclohexyl (3-(N-piperidyl)-ethyl ketone (BP 115° to 117°C/1 mm) in 125 ml of dry ether. The mixture was allowed slowly to come to room temperature, refluxed for one hour, and then poured into ice containing 80 ml of concentrated hydrochloric acid. Ammonium chloride (100 g) and 200 ml of concentrated ammonium hydroxide were added and the organic layer was separated. After drying and removing the solvent, the residue was distilled under reduced pressure. The base distilled at 158° to 170°C (1 mm) and solidified. Upon recrystallization from methanol it melted at 112° to 113°C. 

Kagi, H. and Miescher, K. New synthesis of 4-phenyl-4-piperidyl alkyl ketones and related compounds with morphinelike action, Helv. Chim. Acta 1949, 32, 2489-2507. 

Perhydro-oxazolo[3,4- ]pyridines have long been prepared by condensation between the appropriate piperidyl-2-carbinol and an aldehyde or ketone. For example, the antidepressant spiropiperidine derivative (135) is obtained by the reaction between a-phenyl-2-piperidine methanol and N-benzyl-4-piperidone (81USP4260623). Perhydro-oxazolo[3,4-a]pyridin-3-one (136) is obtained by phosgenation of 2-(hydroxymethyl)piperidinium p-toluene sulfonate followed by cyclization of the resultant chloroformate salt by treatment with triethylamine in dichloromethane. This ring system... 

Dyclonine, i-(4-8utoxyphenyl)-3 - (f -piperidinyl>-l-propanone 3-piperidino-4f -butoxypnopiophenone 0-piper-idinoethy) -4 butoxy pheny 1 ketone 4-butoxy-/)-piperidino -propiophenone 4-n-butoxy -0 -(1 -piperidyl)propiophenone 4-butoxyphenyt piperidineefhyl ketone 2-(I -piperidyDethyl p- but oxy phenyl ketone. C H NO mol wt 289.43. C 74.70%, H 9,40%. N 4.84%, O 11,05%. Prepd from p-but-oxy acetophenone by condensation with formaldehyde and piperidine hydrochloride Pofft, Chem, Tech, (Berlin) 4, 241 (1952), C.A. 47, 10531 (1953), Compare Falicain,... 

N.N -Bis-[4-oxy-benzyl]-pipera in 23,11. 6-Athoxy-3-[4-athoxy-phenyl]-1.2.3.4-tetrahydro-cbmaaolin 23 U 319. 2.5-Eis-[4-oxy-benzyl]-pipenuiln 23 II396. 3.6-Dioxo-l. 5. l".6"-tBtramethyl-4. 4 -diatbyl.3-d>dihydro [dipyrrolo-2. 3 1.2 2".3 4.5.benMl] 24 1 363. jJ-[Piperidyl- 4)]- thyl -[6-methoxy-ohinolyl-(4)]-keton 26II17. 4.6-Dimethyl-l-benzyl-45.6.7-tetrahydro-indazol-carbons ure-(3)-methylester 25 II128. 

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