3-(1-Piperidinylmethyl)phenol

In a reaction flask equipped with a stirrer, a condenser and a thermometer, 2.4 g of 3-hydroxybenzaldehyde was added, It was dissolved in 40 mL of formic acid, stirred, 4.2 g of piperidine was added at less than 60 ° C and heated to 110 ° C for 2 h after completion of the addition (TLC showed complete reaction).Cooled to 15 ° C after dilution with 150mL water, add 0.1g activated carbon decolorization, filtration, The solution was adjusted to pH 8.5 with a 12percent ammonia solution and crystallized at 10 ° C. The crystals were filtered off, washed with water and dried to give intermediate III-1 and yellow crystals 3.0 g in 78percent yield.Preparation 1 REFERENCE Add 1750 g of water to the reaction flask, cool to 10-15 °C, and add 500 g with stirring.(About 5.000 mol) concentrated sulfuric acid, controlled temperature below 30°C. After dropping, After cooling to 15° C., 475 g (2.50 mol) of Compound 7 prepared in was added, and the mixture was stirred and completely dissolved. After cooling to 0° C. or lower, an aqueous solution containing 181 g (2.63 mol) of sodium nitrite was added dropwise.The temperature is controlled below 5°C.After completion of the dropwise addition, the incubation temperature is below 5°C for 0.5 hr. After TLC confirms that all reactions of compound 7 have been completed, Spare (stock solution 1).To another reaction flask was added 1250 g of water, and 375 g (about 3.75 mol) of concentrated sulfuric acid was added dropwise.After the dropwise addition was completed, heating was performed at a temperature of 75°C to 80°C. The stock solution 1 was added dropwise via a dropping funnel.The control temperature is 80 °C ± 5 °C. After the addition, securityThe reaction was carried out at a temperature of 80° C. to 85° C. for 6 hours to 8 hours, and the reaction was monitored by TLC. Until the diazonium salt disappears.After confirming the completion of the reaction, the reaction system is cooled to about 30°C.Then, 500 g of methanol was added, and about 1350 g (about 19.8 mol) of ammonia water was added dropwise, and the temperature was controlled below 60° C., and the pH was adjusted to be 9 to 10 (solids were precipitated during the alkalizing with ammonia).After the adjustment is completed, the system is cooled to 10° C. or less, and the crystallization is maintained for 3 to 4 hours. Filter, 60-80 °C blast drying. Light brown compound 1 was obtained with a dry weight of 450 g (theoretical amount: 477.45 g); yield: 94.3percentTo an oil obtained in the preceding step, 200 ml of methanol and 40 g of 40percent hydrobromic acid were added, Heating to reflux reaction 3h, after the end of the reaction to recover methanol solvent, and add 200ml of water, then the inorganic alkali solution adjusted to pH 7, To obtain an off-white solid, and finally purified by ethanol to give 98.5 g of the desired product, purity 99.6percent, yield 71.4percent(1) To an oil obtained in the preceding step, 200 ml of methanol and 40 g of 40percent hydrobromic acid were added, Heating to reflux reaction 3h, after the end of the reaction to recover methanol solvent, and add 200ml of water, then the inorganic alkali solution adjusted to pH 7, To obtain an off-white solid, and finally purified by ethanol to give 98.5 g of the desired product, purity 99.6percent, yield 71.4percentAdd 750 g of dimethyl sulfoxide to the reaction flask.420 g (2.196 mol) of compound 1 (prepared in Example 3) are added, Add 340g (8.5mol) of sodium hydroxide, heat, raise the temperature to about 90 °C, add 14g of potassium iodide, Under stirring, 340 g (2.615 mol) of 3-chloropropylamine hydrochloride was added in portions, and the reaction was incubated at 100-110° C. for 20 hr.After confirmation of the reaction, 1000 g of water was added, pH=10~11 was adjusted with concentrated hydrochloric acid, and the mixture was stirred for about 1.5 hr. The mixture was allowed to stand for liquid separation. The aqueous phase was extracted once with 800 g of toluene. The organic phase was combined and used 50 kg of sodium chloride. The aqueous solution was washed once, and the liquid was separated. The organic solvent was concentrated and the solvent was weighed to obtain 500 g of an oil (theoretical amount: 545.38 g). Yield: 91.7percent.

Molecular Weight:191.27
XLogP3:2.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:191.131014166
Monoisotopic Mass:191.131014166
Topological Polar Surface Area:23.5
Heavy Atom Count:14
Complexity:166
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes