This is the classic way to make prodine. Although this is rather old stuff [JACS (1947), p 911 - 914], the article is very good (nice descriptive procedure):
Synthesis of 1,3-dimethyl-4-phenyl-4-hydroxypiperidine
One liter of dry ether and 15 g of Li wire cut in to small pieces were placed in a 3-liter RB flask provided with a condenser, stirrer, and dropping-funnel. Bromobenzene (172 g) was placed in the dropping-funnel and 10 ml added at one time to the flask. Gentle warming was employed until the reaction started and then the bromobenzene was added from the dropping-funnel at such a rate that the ether refluxed vigorously. At the end of the reaction the dropping-funnel was rinsed with 100 ml of ether and the flask cooled to -5 °C. One hundred twenty-seven grams of 1,3-dimethyl-4-piperidone was added slowly from the funnel, maintaining the temperature at -5 °C. After the addition, the contents were stirred for 1 hour at room temperature. The flask was cooled in an ice-bath and 200 ml of water was added slowly from the funnel with continued stirring. The ether layer was separated and dried over K2CO3.
After the removal of the ether the residue was distilled in vacuo and the fraction boiling at 130 °C / 2 mm Hg was collected. This product was dissolved in 300 ml of n-hexane (Skellysolve B), and on standing in the ice-box the product crystallized, yielding 150 g of colorless crystals, m.p. 72 - 85 °C. This is a mixture of diastereomeric alcohols.
Synthesis of 1,3-dimethyl-4-phenyl-4-propionoxypiperidine
1,3-dimethyl-4-phenyl-4-hydroxypiperidine (229 g) was dissolved in a mixture of 350 ml of pyridine and 350 ml of propionic anhydride. The solution was refluxed for 3 hours and the solvents were distilled of in vacuo from a steam-bath using a water-pump. The residue, after cooling, was mixed with 200 ml of water and basified with 20 % NaOH solution to bring the pH to 9 - 10. The separated oil was extracted with ether, the ether solution dried over K2CO3, filtered, and hydrogen chloride gas bubbled in until no more hydrochloride separated. The solid, after drying in a vacuum dessicator ofer NaOH, was crystallized from about 600 ml of acetone containing a little methanol. One hundred forthy-five grams of colorless crystals, m.p. 212 - 214 °C, was obtained in the first crop. This fraction is dl-alpha-1,3-dimethyl-4-phenyl-4-propionoxypiperidine hydrochloride. The filtrate was concentrated to 250 ml and allowed to stand in the ice-box overnight. A second crop of crystals was obtained which on recrystallization three times from acetone melted at 190 - 192 °C, yield: 107 g. This is dl-beta-1,3-dimethyl-4-phenyl-4-propionoxypiperidine. hydrochloride.
Just One Fix