7246-14-2

Antibacterial.

ChEBI: Methicillin sodium monohydrate is a hydrate. It contains a methicillin sodium.

To a stirred suspension of 6-aminopenicillanic acid (540 g) in dry alcohol-free chloroform (3.75 liters) was added dry triethylamine (697 ml), and the mixture stirred for 10 minutes at room temperature. It was then cooled in a bath of crushed ice while a solution of 2,6-dimethoxybenzoyl chloride (500 g) in dry alcohol-free chloroform (3.75 liters) was added in a steady stream over 20 minutes. When all the acid chloride had been added the cooling bath was removed and the mixture stirred for 1 hour at room temperature. The mixture was stirred vigorously and sufficient dilute hydrochloride acid (2.3 liters of 0.87 N) was added to give an aqueous layer of pH 2.5. The mixture was filtered, the layers separated, and only the chloroform layer was retained.
This was stirred vigorously while further dilute hydrochloric acid (0.69 liter of 0.87 N) was added to give an aqueous layer of pH 1. The layers were separated and again only the chloroform layer was retained. Then the chloroform layer was stirred vigorously while sufficient sodium bicarbonate solution (3.2 liters of 0.97 N) was added to give an aqueous layer of pH 6.7 to 7.0. The layers were separated and both were retained. The chloroform layer was stirred vigorously while sufficient sodium bicarbonate solution (50 ml of 0.97 N) was added to give an aqueous layer of pH 7.7, and again the layers were separated. The two bicarbonate extracts were combined, washed with ether (1 liter), and then concentrated at low temperature and pressure until the concentrate weighed 1,415 g.
The concentrate was treated with dry acetone (22 liters), the mixture well mixed, and then filtered to remove precipitated solid impurities. Further dry acetone (4 liters) was added to the filtrate, then the product started to crystallize slowly. Crystallization was allowed to proceed at a temperature between 0° and 3°C for 16 hours and then the product (563 g) was collected by filtration. Dry ether (7.5 liters) was added to the filtrate, and after several hours a second crop (203 g) of solid was collected. The two crops were combined to give sodium 2,6-dimethoxyphenylpenicillin monohydrate (766 g, 73%) as a white crystalline solid.