preparation method of 4-pyridinemercaptoacetyl chloride hydrochloride_industrial additives

background and overview of the preparation method of 4-pyridinemercaptoacetyl chloride hydrochloride

4-pyridinemercaptoacetyl chloride hydrochloride can be used as a pharmaceutical synthesis intermediate.

preparation method of 4-pyridinemercaptoacetyl chloride hydrochloride

4-pyridinemercaptoacetyl chloride hydrochloride is prepared as follows:

1) 4-pyridylmercaptoacetic acid: place sodium hydroxide (88, 4, 9, 2, 21 mol) and 600-m1 of water in an endpage: 3 flask equipped with a condenser. add 80-mercaptoacetic acid (76, 79, 0, 67 mol) under stirring, and then add 4-chloropyridine hydrochloride (100 g, 0.67 mol). the mixture was heated at reflux temperature for 4 hours with stirring. approximately 5 g of cooled decolorizing carbon was added to the resulting solution at 80°c. continue stirring for 5 minutes, then filter using filter aid. the r solution was acidified to ph 4.5 by adding acetic acid. the resulting slurry was cooled to 5°c and collected by filtration. 100 ml of solid! wash and dissolve the wet filter cake in 6nhc, 200m, g and 500ml of methylpyridine in water. the clear solution is about 200ml of 10% sodium hydroxide! neutralize to ph5. the slurry was cooled to 5°c, collected on a filter and washed with 200 ml water. the solid was then washed with isopropanol 100rrle. the product 4-pyridylthioglycolic acid was dried at room temperature at 50 °c to give approximately 829 (73). melting point 267-268℃ (decomposition). literature value: mp270°c

2) 4-pyridinemercaptoacetyl chloride hydrochloride: 7-aminocephalosporin acid (10 (1°3.68mol)) was slurried in dichloromethane 251. cool the slurry to 0°c (cool and dry). first add triethylamino (1768m, j, 12.7mol) to the slurry, obtain a complete solution in about 10 sodium carbonate minutes, cool the solution to 110°c and add 4-pyridylmercaptoacetyl chloride hydrochloride [will 4-pyridylmercaptoacetic acid (100p, 5.9 mol) was slurried in dichloromethane 41 in vessel 501 equipped with a condenser and the slurry was saturated with dry hydrogen chloride gas for 20 minutes. stir slowly and add phosphorus pentachloride (1550l, 7.42 mol) in portions over 10-20 minutes. the slurry was diluted, and after 1 hour, the oil phase was observed as the lower layer, and the oily slurry was stirred at 25°c for another 1 hour. the reaction mixture was warmed to slight reflux and hydrogen chloride gas was stirred for 2 hours. the oil layer crystallized during this time and a further 341 dry methylene chloride was added over 2 hours while continuing to reflux slightly. the crystal slurry is cooled once every 1 hour at 25°c. then cool at 0°c for about 8 hours. filter and wash the solid crystalline material with dichloromethane, taking care to prevent moisture, and vacuum dry on the solid cake p2o. 4-pyridylmercaptoacetyl chloride hydrochloride is obtained in a yield of about 80% and a purity of at least 85%.