Preparation method for (R)-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid, derivatives thereof and levo-praziquantel

A method for preparing a compound represented by formula (I),

• wherein, in the formula (I), R1 and R2 are independently selected from hydrogen, C1-C6 alkyl, and C1-C6 alkoxy,
• wherein the method comprises:
• using racemate of an ester of the compound of formula (I) as substrate and reacting under catalysis of immobilized lipase to produce the compound of formula (I),
• wherein the method is performed by using a circulating fluidized bed reactor, the circulating fluidized bed reactor comprises an external circulation system and a reaction column, wherein the immobilized lipase is arranged in the reaction column, the method comprises circulating a substrate solution comprising the substrate between the external circulation system and the reaction column;
• conducting a reaction of a first batch of the substrate;
• taking out the first batch of reaction mixture after the completion of the reaction of the first batch of the substrate, and then adding a second batch of the substrate to continue the reaction;
• taking out the second batch of reaction mixture after the completion of the reaction of the second batch of the substrate, and then adding a third batch of the substrate to continue the reaction,
• wherein taking out a third batch of reaction mixture after the completion of the reaction of the third batch of the substrate, and then adding a fourth batch of the substrate to continue the reaction, and so on, to prepare n batches of reaction mixtures in total, the n is greater than or equal to 5,
• wherein in the substrate solution, concentration of the racemate of the ester of the compound of formula (I) is 9.5-10.5 g/L,
• wherein addition amount ratio of the immobilized lipase to the substrate solution is 2.0-3.5 g/L, and
• wherein flow rate of the substrate solution in the circulating fluidized bed reactor is 0.40-0.45 m/s;
• and
• making the substrate solution flow through the reaction column from bottom to top,
• wherein the reaction column comprises a hollow reaction tube extending in an up and down direction, and a jacket covering an outside of the hollow reaction tube, the reaction column optionally comprises a telescopic piston for controlling a volume of liquid inside the hollow reaction tube, and the hollow reaction tube is in communication with the external circulation system, and
• wherein upper and lower ends of the hollow reaction tube are respectively provided with a filter membrane for preventing the immobilized lipase from flowing out of the reaction column.