Preparation method of 4-[(4-chlorphenyl)-2-pyridylmethoxy]-1-piperidine carboxylate

[0072] The preparation of embodiment one (4-chlorophenyl)-2-pyridone

[0073]

[0074] In a 1-liter four-necked flask, add 370 ml of dichloromethane, 2-pyridine formate (123 g, 1.0 mol) g, dimethylformamide (2 g), and dropwise add thionyl chloride (142.8 g, 1.0 mol), stirred at 15-20° C. for 1 hour after the addition, heated and refluxed for 6 hours, and the reaction was completed. The dichloromethane and excess thionyl chloride were concentrated under reduced pressure to obtain 2-picolinoyl chloride, and the next feeding was carried out according to the theoretical amount.

[0075] Add chlorobenzene (566g, 5.0mol), aluminum trichloride (153g, 1.15mol) in 2 liters of four-necked flasks, add 2-picolinoyl chloride dropwise below 20 ℃ of temperature control, heat up 40 ℃ of reaction 4 hours after adding . After the TLC reaction was completed, the temperature was lowered by 10°C. Pour into ice water, control the temperature below 10°C, stir for 10 minutes, and separate the liqu

[0076] The preparation of embodiment two (4-chlorophenyl)-2-pyridinemethanol (formula I)

[0077]

[0078] In a 2-liter four-necked flask, add 650 ml of methanol, (4-chlorophenyl)-2-pyridone (217 g, 1.0 mol), control the temperature below 15 °C, add sodium borohydride (38 g, 1 mol) in batches, and finish adding Then slowly heat up to 20°C, keep warm for 2 hours, after the reaction is completed, add 1300g of water below the temperature of 10°C, cool down to 0°C, keep warm for 2 hours, filter to obtain 235g of solid wet weight, and dry to obtain (4-chlorophenyl)-2 -197 g of pyridinemethanol, yield 90.1%. 1 H-NMR (CDCl 3 ) δppm 5.79(1H,s), 7.13-7.14(2H,d), 7.18-7.21(1H,t), 7.25-7.27(2H,d), 7.50-7.57(1H,d), 7.67-7.70(1H , t), 8.61-8.62 (1H, d)

[0079] Examples three to seven Preparation of 4-[(4-chlorophenyl)-2-pyridylmethoxy]-1-carboxylic acid ethyl ester (formula III, R=Et)

[0080]

[0081] Add acetonitrile and ethyl 4-hydroxypiperidine-1-carboxylate to a 2-liter four-necked flask, add trifluoroacetic anhydride dropwise below 15°C under temperature control, heat up to 20-25°C after adding, keep the temperature for 1 hour, and monitor 4 by TLC. -Hydroxypiperidine-1-carboxylic acid ethyl ester no residue. Add (4-chlorophenyl)-2-pyridinemethanol, then add catalyst boron trifluoride acetonitrile, heat up at 20-30° C., keep the temperature for 3 hours, and the TLC reaction is completed. Aqueous sodium hydroxide solution was added dropwise under temperature control to 40°C to adjust the pH to 9, and acetonitrile was concentrated under reduced pressure at temperature control of 70-80°C. After concentration, add 300 grams of water and 500 grams of toluene, stir evenly, separate the liquids, and concentrate the toluene ph