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%.
