The invention relates to the technical field of medicines, in particular to a chiral purification process of a loratinib intermediate, which comprises the following steps: S1, carboxyl esterification: adding 4-fluoro-2-(1-ethoxyl)-N, N-bis (1-methylethyl)
benzamide into a catalytic
mixed solution, controlling the temperature to 25-40 DEG C, adding
benzoic anhydride to react for 5-7 hours, detecting the reaction of raw materials by central control TLC (
Thin Layer Chromatography), filtering, washing, and
drying to obtain the loratinib intermediate. Cooling, performing suction
filtration, leaching and
drying to obtain a compound III; s2,
enzyme catalysis: adding the obtained compound III into an
organic solvent, in a
nitrogen atmosphere, controlling the temperature at 35-40 DEG C, adding
lipase, stirring and reacting until the
system does not release heat any more, continuously stirring for 1-2 hours, cooling to
room temperature, adsorbing and filtering the obtained reaction liquid, adjusting the pH value to 8-10, extracting and separating liquid, washing, and performing rotary
evaporation to obtain a crude product, and purifying through an enzymatic solution to obtain a compound IV; s3,
hydrolysis and purification: adding the compound IV into an alcoholic solution, mixing, dropwise adding alkali liquor, stirring and reacting for 1-2 hours at
room temperature, tracking the reaction by TLC, adding a saturated
sodium bicarbonate solution, extracting, washing,
drying, filtering and carrying out rotary
evaporation to obtain the 4-fluoro-2-[(1S)-1-ethoxyl]-N, N-bis (1-methylethyl)
benzamide. The chiral purification method of the loratinib intermediate is mild in reaction condition, low in cost, high in
catalytic efficiency, good in
stereoselectivity, simple and convenient in post-treatment operation, easy to industrially catalyze a chiral compound resolution means and capable of being used for industrial production.