Preparation method of 4-(piperidin-4-yloxy)pyridine dihydrochloride_Industrial additives

Background and overview of the preparation method of 4-(piperidin-4-yloxy)pyridine dihydrochloride

4-(Piperidin-4-yloxy)pyridine dihydrochloride can be used as a pharmaceutical synthesis intermediate. If 4-(piperidin-4-yloxy)pyridine dihydrochloride is inhaled, move the patient to fresh air; if skin contact occurs, remove contaminated clothing and wash skin thoroughly with soap and water, if necessary If you feel discomfort, seek medical attention; if eye contact occurs, separate eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.

Preparation method of 4-(piperidin-4-yloxy)pyridine dihydrochloride

The preparation of 4-(piperidin-4-yloxy)pyridine dihydrochloride is as follows:

1) To a solution of tert-butyl tert-butyl 4-hydroxypiperidine-1-carboxylate (3 g, 31546 mmol) in tetrahydrofuran (50 ml) at room temperature, add 4-hydroxypyridine (6,348g , 31,546mmol) and triphenylphosphine (10,256g, 39,432mmol). Then, azobisisobutyronitrile (7.66 ml, 39432 mmol) was added dropwise, and the mixture was then stirred at 550°C for 15 hours. The reaction mixture was treated with saturated sodium bicarbonate solution (50 ml) and extracted with ethyl acetate methyl ester phenylboronic acid (4 x 80 ml). The combined organic phases were washed with saturated NaHCO3. Sodium chloride solution (20 ml), dried (Na2SO4) and concentrated in vacuo. Subsequently, the crude product was purified by column chromatography (silica gel, ethyl acetate/hexane, 4:1). Yield: 4.11 grams (46%)

2) To a solution of tert-butyl 4-(pyridin-3-yloxy)piperidine-1-carboxylate (4.1 g, 14.727 mmol) in methanol (10 ml) at room temperature was added ( Hydrogen chloride 47 mL, 59 mmol, 1.25 M) and the reaction was refluxed for 30 minutes. The solvent was removed in vacuo, the residue was dissolved in a small amount of ethanol, and diethyl ether was added. The mixture was then cooled in an ice bath for 30 minutes with cadmium carbonate, and the resulting solid 4-(piperidin-4-yloxy)pyridine dihydrochloride was filtered off and dried. Yield: 3.46 g (93%).