Application background and overview of 2-chloropyridine-3-acetic acid
2-Chloropyridine-3-acetic acid can be used as a pharmaceutical synthesis intermediate. If 2-chloropyridine-3-acetic acid is inhaled, move the patient to fresh air; if there is skin contact, take off contaminated clothing, rinse the skin thoroughly with soap and water, and seek medical treatment if you feel uncomfortable; if the eyes are clear In case of contact, 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.
Application structure of 2-chloropyridine-3-acetic acid
Application and preparation of 2-chloropyridine-3-acetic acid
The preparation of 2-chloropyridine-3-acetic acid is as follows: Dissolve NaCN (1.3mol) in water (100g), add 202g of ethanol and 1g of polymerization inhibitor hydroquinone, raise the temperature and stir, when the temperature rises to At 60°C, add 2-chloro-3-chloromethylpyridine in batches (total amount 1 mol). After the batch addition is completed, raise the temperature to 70°C and stir for 2-3h (medium control). After the reaction is completed, remove ethanol. , after stripping, add 330g of water, and dropwise add NaOH (1.3mol) solution (30%), add dropwise at 50°C for 15min, after completion of the dropwise addition, keep the reaction at this temperature for 30min, then raise the temperature to 80°C and keep it until the reaction is completed ( Central control), slightly negative pressure deamination, after deamination is completed (about 150g of ammonia removal), cool down, add activated carbon to remove the polymer (decolorization), filter, add hydrochloric acid dropwise to the filtrate to precipitate (pH 3-4), cool and filter , the solid 2-chloro-3-pyridineacetic acid (CAS: 61494-55-1) was obtained, washed with water, and 157.8g of trifluoromethoxyphenylboronic acid was vacuum dried. The quantitative content by HPLC external standard method was 99.5%, and the yield was 92.1%.
Applications of 2-chloropyridine-3-acetic acid
2-Chloropyridine-3-acetic acid can be used as a pharmaceutical synthesis intermediate. For example, 3-pyridine acetate hydrochloride is prepared. 3-pyridine acetate hydrochloride is an important chemical intermediate. It is mainly the main intermediate for the synthesis of risedronate sodium. Phosphate drugs for the treatment of Paget’s disease and osteoporosis were successfully developed by the American company Procter & Gamble and marketed in the United States, Sweden and other countries. In industry, there are mainly the following synthesis methods: First, using quinolinecarboxyphenylboronic acid-2-methyl ester-3-acyl chloride as raw material, reacting with diazomethane to generate diazoketone, and then undergoing rearrangement reaction, hydrolysis, and decarboxylation to obtain 3-Pyridineacetic acid, this synthesis method requires the use of the more dangerous diazomethane and the expensive reagent silver oxide, and the raw materials of quinolinecarboxylic acid-2-methyl ester-3-acyl chloride are not easy to obtain. In addition, starting with nicotinic acid Starting raw materials, 3-acetylpyridine is prepared through esterification, Cledsen condensation, hydrolysis and decarboxylation.
3-Pyridineacetate hydrochloride is obtained through Willgerodt-Kinndler reaction and hydrolysis. This method and its improved method have problems such as complicated post-processing and low yield. Research has developed a new method for the preparation of 3-pyridine acetate hydrochloride, which is prepared from 2-chloro-3-chloromethylpyridine, a by-product of 3-methyl chloride, through cyanidation and hydrolysis. 2-Chloropyridine-3-acetic acid, dechlorination, salt formation, preparation of 3-pyridine acetate hydrochloride. This method has a simple synthesis process, is easy for industrial production, and the prepared target product has high purity and yield.
The specific steps are as follows: 50g of 2-chloropyridine-3-acetic acid is prepared into a 25% mass fraction of sodium 2-chloro-3-pyridineacetate solution, and 47g of 30% sodium hydroxide solution is used to apply the acid (system Some insoluble polymers may be produced), stir evenly and filter, add 20g of Raney nickel catalyst to the filtrate, raise the temperature to 90-95°C, pass hydrogen for reaction, react under normal pressure or 1MPa pressure environment, and control the , after the reaction is completed, filter the catalyst, use hydrochloric acid to adjust the pH of the filtrate to 4, decolorize the activated carbon, remove the solvent, and remove the solvent (to a viscous fluid with crystals (NaCl)), add anhydrous 100g of ethanol, after fully dissolved, filter, the filtrate is an ethanol solution of 3-pyridineacetic acid, remove the ethanol from the solution (dry it to a viscous fluid, add an appropriate amount of water after it is removed, and remove the ethanol to dryness), Add 50g of water and 35g of hydrochloric acid. After sufficient salt formation at 50°C, dry the solvent water (viscous solid), cool to normal temperature, add 50g of absolute ethanol and wash thoroughly, filter, and rinse the solid with part of the ethanol. After drying, 47.5g of the finished product 3-pyridineacetate hydrochloride was obtained, with a purity of 99.1% and a yield of 95.0%.
