TECHNOLOGY FOCUS - ORGANIC CHEMISTRY - Preferred Method: The splitting of racemic 1-phenylethanol derivatives, comprises reacting racemic 1-phenylethanol derivative TM1 (racemate) with 0.5-0.8 eq. wt. (preferably 0.6 eq. wt.) tert-butoxycarbonyl (Boc)-L-proline in 3 ml/g dichloromethane solvent at 0 degrees C to room temperature (preferably 0 degrees C), then adding a catalyst, heating to 20 degrees C naturally and reacting, where the catalyst is mixed solution of 0.6-1 eq. wt. (preferably 0.8 eq. wt.) 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCl) and 0.1-0.2 eq. wt. (preferably 0.15 eq. wt.) p-toluenesulfonic acid, and the reaction time is 2 hours, then carrying out vacuum distillation at a vacuum degree of 10 plus minus 2 mmHg and temperature of 120 plus minus 10 degrees C to obtain crude product, recrystallizing the crude product with 0.5 ml/g n-hexane, dissolving at room temperature, and then cooling to -20 degrees C to separate out the product. The splitting byproduct mixture by hydrolysis, comprises dissolving obtained byproduct mixture (BP1, BP2 and BP3) in methanol solvent (3 ml/g of raw material), adding 2-5 eq. wt. (preferably 3 eq. wt.) saturated aqueous sodium hydroxide solution, and reacting at 25 degrees C for 1-2.5 hours (preferably 1.5 hours). The conversion of the configuration of byproduct, comprises carrying out Mitsunobu reaction using Boc-D-proline, triphenylphosphine and azo reagent to convert configuration of BP2, where R-type BP2 is converted into S-type BP2, the process utilizes 1-1.3 eq. wt (preferably 1.2 eq. wt.) Boc-D-proline as hand-shaped conversion reagent, 1.2-1.8 eq. wt. (preferably 1.6 eq. wt.) diethyl azodicarboxylate as active reagent, and 1.2-1.8 eq. wt. (preferably 1.4 eq. wt.) triphenylphosphine as oxygen acceptor, tetrahydrofuran (10 ml/g of BP2) as a solvent, weight ratio between Boc-D-proline and diethyl azodicarboxylate is 0.75:1, and the reaction temperature is 20 degrees C and the reaction time is 2-5 hours (preferably 3 hours), then dissolving obtained reaction of mixture (BP4 and TM2) in methanol solvent (3 ml/g of raw material), adding 2-5 eq. wt. (preferably 3 eq. wt.) saturated aqueous sodium hydroxide solution, reacting at 25 degrees C for 1-2.5 hours (preferably 1.5 hours) to obtain crude product, and recrystallizing the crude product to obtain (S)-1-(2,6-dichloro-3-fluorophenyl)ethanol (TM2). The aromatic ring bromination, comprises reacting (R)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-2-amine with 1-1.5 eq. wt. (preferably 1 eq. wt.) N-bromosuccinimide in carbon tetrachloride solvent (5.5 ml/g of raw material) at 0-20 degrees C (preferably 0 degrees C) for 0.5 hour to obtain (R)-5-bromo-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-2-amine, where the reaction end point is detected by thin layer chromatography. The method comprises (a) carrying out reduction of 1-(2,6-dichloro-3-fluorophenyl)ethanone to obtain racemic 1-(2,6-dichloro-3-fluorophenyl)ethanol, spitting the racemic 1-(2,6-dichloro-3-fluorophenyl)ethanol using N-(tert-butoxycarbonyl)-L-proline, p-toluenesulfonic acid catalyst and condensing agent 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride to obtain S-type and R-type alcohol, then separating obtained product and purifying to obtain (S)-1-(2,6-dichloro-3-fluorophenyl)ethanol (TM2), then hydrolyzing the split-product using sodium hydroxide, carrying out Mitsunobu reaction of hydrolyzed product using triphenylphosphine and diethyl azodicarboxylate, hydrolyzing with sodium hydroxide, separating and purifying to obtain crystalline (S)-1-(2, 6-dichloro-3-fluorophenyl)ethanol (TM2), then etherifying, converting configuration of obtained product to obtain (R)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-2-nitropyridine (TM3), reducing TM3 to obtain (R)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridine-2-amine (TM4), reacting TM4 with N-bromosuccinimide in carbon tetrachloride solvent to obtain (R)-5-bromo-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridine-2-amine (TM5), reacting TM5 with tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidin-1-carboxylate to obtain tert-butyl 4-(4-(6-amino-5-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)-1-piperidinecarboxylate (TM6), then carrying out acid hydrolysis of TM6 and re-crystallizing to obtain 3-((1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(4-piperidinyl)-1H-pyrazol-4-yl)-2-pyridinamine i.e. crizotinib.