N,N-Dimethylaniline → 2-Naphthalenesulfonic acid

Participants

Reaction Steps

202 mg. (0.002 mole) of triethylamine in 1 ml. of anhydrous dichloromethane and 134 mg. (0.0011 mole) of N,N-dimethylaniline in 1 ml. of anhydrous dichloromethane are added under an atmosphere of nitrogen and at ambient temperature to a suspension of 256 mg. (0.001 mole) of 6'-amino-spiro[cyclohexane-1,2'-penam]-3'-carboxylic acid (prepared as indicated in Example 3.1) in 4 ml. of anhydrous dichloromethane. The mixture is stirred magnetically for 20 hours at ambient temperature and thus the solubilization is practically complete. The mixture is cooled to 12°-15° C. and 217 mg. (0.002 mole) of trimethylchlorosilane in 1 ml. of anhydrous dichloromethane are added dropwise. A white precipitate is formed which dissolves when the temperature comes back to 20° C. The reaction mixture is heated under reflux for 45 minutes. After this mixture has been cooled to -10° C., 206 mg. (0.001 mole) of 2-phenylglycyl chloride hydrochloride are added in portions over a period of 20 minutes. The mixture is stirred for half an hour and then placed in a refrigerator for 2 hours. The reaction mixture is then poured into 5 ml. of water, decanted and the aqueous phase, which has a pH of 1.7, is made up to 10 ml. and the pH adjusted to between 1.8 and 2 with 1N hydrochloric acid. The resulting white solid is filtered off. The filtrate is cooled to 2° C. and 240 mg. of (0.00125 mole) naphtalenesulfonic acid in 1 ml. of water are added thereto. The pH is adjusted to between 1.5 and 1.8. A white solid crystallizes out and stirring is continued for some hours at 2° C. The solid is filtered off, washed with iced water and with ethyl acetate and then dried in vacuo. 300 mg. of the 2-naphtalenesulfonic acid salt of 6'-(2"-amino-2"-phenylacetamido)-spiro[cyclohexane-1,2'-penam]-3'-carboxylic acid are thus obtained. The base is liberated by adding 52 mg. (0.0005 mole) of triethylamine and treating the mixture at about 70°-80° C. for 15 minutes. The resulting product is filtered off and washed with a mixture of isopropanol and water (85:15). 60 mg. of 6'-(2"-amino-2"-phenylacetamido)-spiro[cyclohexane-1,2'-penam]-3'-carboxylic acid are thus obtained. M.P. 211°-213° C. (decomposition). 40 mg. of this acid are converted into the sodium salt by treatment with a solution of 8.7 mg. of sodium hydrogen carbonate in 3 ml. of water.

Provenance & Evidence