1-[(2,4-difluorophenyl)methyl]piperidin-4-one

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 28.20 g (0.125 mol) of 1-(2,4-difluorobenzyl)-4-piperidone crude product was added to a reaction bottle, to which 200 mL of toluene was added. The reaction was heated and stirred at 80° C. in an oil bath, and to the reaction 29.60 g (0.135 mol) of trimethylsulfoxide iodide and 0.60 g (0.0018 mol) of tetrabutylammonium hydrogen sulfate were added in sequence and then 11.40 g (0.285 mol) of sodium hydroxide dissolved in 60 mL of aqueous solution was added dropwise under stirring. After the addition, the reaction was continuously stirred at bath temperature of 80° C. overnight. On the next day, the reaction was cooled, washed with water twice, extracted with a small amount of toluene, combined and dried, and the solvent was recovered to obtain light yellow liquid 22.00 g (73.6%), i.e., a crude target product, 1H-NMR (CDCl3, ppm) δ: 7.361 (1H, m), 6.76-6.89 (2H, m), 3.597 (2H, d, J=1.12 Hz), 2.651 (2H, s), 2.601 (4H, m), 1.829 (2H, m), 1.545 (2H, m). was added The reaction was heated were added in sequence was added dropwise under stirring After the addition the reaction was continuously stirred at bath temperature of 80° C. overnight On the next day, the reaction was cooled washed with water twice extracted with a small amount of toluene dried the solvent was recovered

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 28.20 g (0.125 mol) of 2,4-difluorobenzyl bromide was weighed, to which 200 mL of dichloromethane was added and then 62.00 g (0.404 mol) of 4-piperidone hydrochloride monohydrate was added under stirring. And then 86.00 g (0.850 mol) of triethylamine was added dropwise at a bath temperature of 30-40° C. under stirring. After the addition, the reaction was heated, refluxed and reacted overnight. On the next day, the reaction was cooled, filtered to removed solid, washed in sequence with dichloromethane and ethyl ether, combined, washed with water and dried, and the solvent was recovered to obtain 61.10 g of crude product (73.3%), 1H-NMR (CDCl3, ppm) δ: 7.31-7.33 (5H, m), 3.56 (2H, s), 2.64 (2H, s), 2.53-2.62 (4H, m), 1.52-1.86 (4H, m); which was used directly in the next step of reaction. was added under stirring After the addition the reaction was heated refluxed reacted overnight On the next day, the reaction was cooled filtered to removed solid washed in sequence with dichloromethane and ethyl ether washed with water dried the solvent was recovered