GENERAL STEPS: 5-(4-hydroxypiperidin-1-yl)-2-thiophenecarboxaldehyde and 3,4-dimethoxybenzeneacetonitrile were placed in a reactor and dissolved in ethanol. After addition of sodium ethoxide, the mixture was stirred under reflux conditions. After completion of the reaction, the reaction mixture was cooled with flowing water for tens of minutes. Water was added to the cooled mixture and stirring was continued for tens of minutes. The precipitated crystals were collected by filtration, washed sequentially with water, ethanol and hexane, and then dried under reduced pressure to give (Z)-2-(3,4-dimethoxyphenyl)-3-[5-(4-hydroxypiperidin-1-yl)thiophen-2-yl]acrylonitrile. Using 5-bromothiophene-2-carbaldehyde (42.30 g) and 4-hydroxypiperidine (67.30 g), an amination reaction was carried out according to Preparation Step 1 to obtain 5-(4-hydroxypiperidin-1-yl)-2-thiophenecarboxaldehyde (yield: 33.00 g, 71%). The prepared 5-(4-hydroxypiperidin-1-yl)-2-thiophenecarboxaldehyde (10.56 g) was subjected to condensation reaction with 3,4-dimethoxyphenylacetonitrile (8.86 g) according to the preparation step 2 to obtain (Z)-2-(3,4-dimethoxyphenyl)-3-[5-(4-hydroxypiperidin-1-yl)thiophen-2-yl]acrylonitrile (yield: 13.50 g, 73%). The obtained (Z)-2-(3,4-dimethoxyphenyl)-3-[5-(4-hydroxypiperidin-1-yl)thiophen-2-yl]acrylonitrile (20.00 g) was dissolved in chloroform (650 mL), and reacted with pyridine (6.41 g) and bromoacetyl bromide (14.13 g) according to Preparation Step 3 (Method A) to obtain bromoacetic acid 1-[5-[(Z)-2- cyano-2 -(3,4-dimethoxyphenyl)vinyl]thiophen-2-yl]piperidin-4-yl ester (yield: 23.00 g, 87%). The prepared 1-[5-[(Z)-2-cyano-2-(3,4-dimethoxyphenyl)vinyl]thiophen-2-yl]piperidin-4-yl ester of bromoacetic acid (2.30 g) was dissolved in chloroform (100 mL), and was reacted with piperidine (533 mg) and triethylamine (658 mg) according to Preparation Step 4 to give (Z)-2-(3,4-dimethoxyphenyl)-3-(5 -(4-hydroxypiperidin-1-yl)thiophen-2-yl)acrylonitrile (Yield: 1.40 g, 60%).
