Alphaprodine hydrochloride

Alphaprodine, l,3-dimethyl-4-phenyl-4-piperidyl propionate hydrochloride (Nisentil , Prisil-idene ), resembles meperidine chemically. Its analgesic and depressant actions are less intense, but more prompt and of shorter duration, than those of morphine. It is a potent, short-acting narcotic 

Alphaprodine hydrochloride is administered by subcutaneous injection in doses of 40 to 60 mg depending upon the weight of the patient. Analgesia occurs within 5 min and lasts about 2 h. Nalorphine is an effective antidote to overdosage. 

Chemical Name cis-1 dlmethy -4-phenyl-4-piperidinol propanoate hydrochloride Common Name - 

The solution of phenyl-lithium is cooled to -20°C and to this a solution of 12.7 grams of 

3-dimethyl-4-piperidone, prepared according to the method of Howton, J. Org. Chem. 

277 (1945), in ether is added dropwise with stirring. After the addition, the stirring is continued for a further 2 hours at -20°C. The lithium complex, 1,3-dimethyl-4-phenyl- 

4-oxylithium piperidine, which forms is soluble in the ether and can be recovered therefrom. To prepare the piperidinol, the lithium complex, while in the reaction mixture is decomposed by the addition of an ice and hydrochloric acid mixture. The acidified layer is separated, basified and extracted with ether. After drying the ether solution and removing the solvent, the residue on distillation in vacuum distills chiefly at 155°C/10 mm, yielding the product, 1,3-dimethyl-4-phenyl-4-hydroxy piperidine, which, on crystallization from n-hexane melts at 102°C. On treatment with propionic anhydride catalyzed with a trace of sulfuric acid, 1,3-dimethyl-4-propionoxy-4-phenyl piperidine is attained. The latter compound can be converted into the hydrochloride salt by reaction with hydrogen chloride. 

The solution of phenyl-lithium is cooled to -20°C and to this a solution of 12.7 grams of 1,3-dimethyl-4-piperidone, prepared according to the method of Howton, J. Org. Chem. 

This salt after crystallization from acetone has a melting point of 209 C. 

Chemical Name cis-1 j-dimethvl-4-phenyl-4i3iperidinol propanoate hydrochloride Common Name — 

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Figure 5.49. Part of the 400 MHz H-NMR spectra of (R,S j-alphaprodine hydrochloride showing the 3-methyl (near 0.8 ppm) and ester methyl (OCH Me, near 1.2 ppm) resonances (a) in D2O alone (b) in D2O plus 1 molar equiv. of f-cyclodextrin (see Figure 5.3 for formula).

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