Overview[1]
(-)Phenylbenzoylcolide is one of the isomers of biphenyl-4-formylcolide and can be used in the synthesis of prostaglandin drugs. Prostaglandins are an important class of endogenous physiologically active substances. They are important mediators in various physiological processes and have high pharmacological activity. Clinically, prostaglandins are all artificially synthesized. Coreylactonephenylbenzoate is a chiral intermediate for the synthesis of PGF2α prostaglandin drugs. Its chemical name is hexahydro-4-(hydroxymethyl)-2-oxo-2H-cyclopenta. [b] Furan-5-yl 1,1′-biphenyl-4-carboxylate, usually including (±)biphenyl-4-carboxylic acid lactone, (-) phenylbenzoyl colic acid lactone ester and (+)biphenyl-4-carboxylicolactone.
Preparation[1]
(1) Add 1.0kg of (-) corylide diol dihydroxy derivative into 10L acetone, add 1L hydrochloric acid solution with a concentration of 2mol/L under stirring, and react at 60°C for 4 hours until the reaction is complete. , lowered to room temperature to obtain a suspended hydrolyzate; add the suspended hydrolyzate to saturated sodium carbonate solution and neutralize to pH = 7 to obtain a suspended neutralized liquid; then stir at a temperature of 40°C for 2 hours, slowly cool to room temperature, and place After 2 hours, a suspended reaction liquid is obtained; filter the suspended reaction liquid, collect the filter cake, and obtain 0.419kg of crude trityl alcohol; collect the filtrate of the suspended reaction liquid, evaporate the solvent acetone under reduced pressure, and cool to room temperature to obtain a suspended aqueous solution , filter, and collect the filter cake to obtain 0.567kg of (-)biphenyl-4-carboxylicolactone crude product;
(2) Add the crude trityl alcohol obtained in step (1) to 4.19L of acetonitrile/ethanol with a volume percentage of 95%:5%, heat and stir until completely dissolved, cool to room temperature, filter, wash, and prepare Trityl alcohol pure product 0.408kg, yield 92.8%, purity 99.65%;
(3) Add the crude (-)biphenyl-4-carboxylicolactone obtained in step (1) to 5.67L of diethyl ether/methanol with a volume percentage of 95%:5%, heat and stir until completely dissolved , cooled to room temperature, filtered, washed, and 0.554kg of (-)biphenyl-4-carboxylicolactone pure product was obtained, with a yield of 93.1% and a purity of 99.51%. (D) Recrystallization of biphenyl-4-formylcorylide: Add the crude biphenyl-4-formylcorylide obtained in step (B) to the heavy biphenyl-4-formylcorylide. Reflux the reaction in the crystallization solvent (double solvent S4/S5) for 1-5 hours, cool to room temperature, filter the precipitated solid, and wash to obtain pure (-) phenylbenzoyl corylide;
Main reference materials
[1][Chinese invention] CN201711468377.X A method for preparing triphenylmethanol and biphenyl-4-carboxylic acidolactone
