Using 4-piperidinic acid as a starting material, N-ethoxycarbonyl-4-piperidinic acid methyl ester was prepared by reacting it with ethyl chloroformate in a one-pot reaction involving esterification and amino protection. This methyl ester was then reacted with magnesium phenyl bromide to prepare N-ethoxycarbonyl-α,α-diphenyl-4-piperidinol, which was finally hydrolyzed with potassium hydroxide to obtain the target compound. This process utilizes inexpensive and readily available raw materials, has a short synthetic route, is simple to operate, and achieves an overall yield of 68.8%.
alpha,alpha-Diphenyl-4-piperidinomethanol is an important organic synthetic substance for the synthesis of diphenyl-4-piperidinomethanol. It is also used as a pharmaceutical intermediate in the preparation of terfenadine and Fexofenadine hydrochloride.
α,α-Diphenyl-4-piperidinemethanol has the appearance of a white to almost white powder to crystals with a melting point of 163 °C. Store at -20 °C.
α-(4-Piperidyl)benzhydrol is a key intermediate in the synthesis of Fexofenadine (F322490). Fexofenadine EP Impurity E.
ChEBI: Diphenyl(4-piperidinyl)methanol is a diarylmethane.
A mixture of 26 g (0.1 mol) of α-(4-pyridyl)-benzhydrol, 1.5 g of platinum
oxide, and 250 ml of glacial acetic acid is shaken at 50-60°C under hydrogen
at a pressure of 40-50 lb/in2. The hydrogenation is complete in 2 to 3 hours.
The solution is filtered and the filtrate evaprated under reduced pressure. The
residue is dissolved in a mixture of equal parts of methanol and butanone and
0.1 mol of concentrated hydrochloric acid is added. The mixture is cooled and
filtered to give about 30 g of α-(4-piperidyl)benzhydrol hydrochloride, MP 283-
285°C, as a white, crystalline substance.
The free base is readily obtained from the hydrochloride salt by treatment
with ammonia and when so obtained has a melting point of 160-161°C.
Frenquel (Marion Merrell
Dow).
