Background and overview[1]
1-(2,3-Dimethylphenyl)piperidine can be used as a pharmaceutical synthesis intermediate. If 1-(2,3-dimethylphenyl)piperidine is inhaled, move the patient to fresh air; if skin contact occurs, remove contaminated clothing and rinse skin thoroughly with soap and water. If discomfort occurs If you feel sick, 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[1]
The preparation of 1-(2,3-dimethylphenyl)piperidine is divided into the following steps:
(1) Preparation of bis(2-chloroethyl)amine hydrochloride (5)
Add thionyl chloride (128 mL, 1.76 mol) to 80 mL of chloroform, stir, and slowly add 68 mL of chloroform-diluted diethanolamine (40 mL, 0.417 mol) dropwise within 1 hour. After the dripping is completed, react at room temperature for 2-5 hours, slowly raise the temperature to 70°C, and then reflux for 0.5-1 hour to complete the reaction. Cool and filter with suction. The filter cake is washed twice with dichloromethane and dried to obtain 66 g of white solid with a yield of 89% and a melting point of 214-215°C (document 207-209°C).
(2) Preparation of 1-phenylpiperazine hydrochloride (7)
Add compound 5 (30g, 0.168mol) to 150mL n-butanol, stir, and slowly add 2,3-dimethylaniline (14.25g, 0.153mol) diluted with 10mL n-butanol dropwise. , refluxed for 30h, then added potassium carbonate (23g, 0.168mol), continued refluxing for 40h and then ended the reaction. Filter while hot to obtain dark red mother liquor, cool and crystallize, filter, wash the filter cake twice with a small amount of n-butanol, dry, and finally obtain 21.59g of white (reddish) solid, with a yield of 71%.
Preparation of (3)1-phenylpiperazine (8)
Dissolve compound 7 (26.0g, 0.115mol) in 250mL water, adjust the pH to about 12 with 40% sodium hydroxide solution, extract with ethyl acetate (2×200mL), and wash once with water and saturated brine respectively. , the organic phase was dried over anhydrous sodium sulfate overnight, filtered, and concentrated under reduced pressure to obtain 20.8 g of 1-(2,3-dimethylphenyl)piperidine as a light yellow oil, with a yield of 95%.
Main reference materials
[1]CN201510817940.4 Hexahydropyrazinoquinoline D3 receptor ligand and its preparation method and use
