To a stirred suspension of 370 mg. (0.002 mole) of 2-(2-thienyl)-malonic acid (Netherlands Patent No. 6805524) in 4 ml. of water is added 532 mg. (0.002 mole) of 6-amino-2,2-dimethyl-3-(O-methylphosphono)penam. The pH is then adjusted to 6.5 using 20% aqueous sodium hydroxide. The resulting solution is cooled to 0° C. and 384 mg. (0.002 mole) of 1-ethyl-3-(3-dimethylaminoprop-1-yl)carbodiimide hydrochloride is added. The solution is stirred for 3.5 hours at 0° C., with the pH maintained between 6 and 7 using 1N hydrochloric acid. At this point, the pH of the solution is then lowered to 2.0 and the mixture is extracted with two 30 ml. portions of ethyl acetate. The combined extracts are dried, and are then concentrated to about 15 ml. To this solution is added a solution of 665 mg. (0.004 mole) of sodium 2-ethylhexanoate in 2.6 ml. of ethyl acetate. The solid which precipitates is filtered, and dried to give 6-[2-carboxy-2-(2-thienyl)acetamido]-2,2-dimethyl-3-(O-methylphosphono)penam as its disodium salt.
