Patent / 1965
Esterification of temperature- or acid-sensitive compounds
Treatment of salts of carboxylic acids or of inorganic oxyacids with alkyl chloroformates at low temps. yielded the mixed anhydride which on addn. of the appropriate alc. gave the ester. To a suspension of 37.2 g. Penicillin G K-salt in 100 g. Me2CO (I), 13 ml. ClCOOEt in 25 ml. I was added; then 13.5 ml. Et2NCH2CH2OH in 25 ml. I was added under ice cooling. After 20 min. 2.71 g. 47.3% HIO3 in 50 ml. I was added to bring the pH to 4.5-5. The ppt. was filtered off, washed with I and Et2O, dried, and then washed twice with H2O to give 74% the iodate of diethylaminoethyl ester of Penicillin G, m. 170-8.degree.. In a similar manner the following compds. were prepd.: chloramphenicol pantothenate; Iodate of diethylamino ethyl 6-aminopenicillanate; chloramphenicol palmitate, m. 89-90.degree., [.alpha.]D 25.degree. (2% in EtOH); methyl gibberellinate, m. 208-9.degree., [.alpha.]D 76deg;; Na prednisolone 21-phosphate, [.alpha.]D 105.degree., .lambda. 239 m.mu., E1%1cm. 306 (MeOH); Na prednisolone 21-sulfate, [.alpha.]D 110.degree., .lambda.max. 239 m.mu. E1%1cm. 312. Na 9.alpha.-fluoro-16.alpha.-methylprednisolone 21-sulfate, [.alpha.[D 80-5.degree. (1% in H2O), .lambda., 238 m.mu., E1%1cm. 292; Na 9.alpha.-fluoro-16.beta.-methylprednisolone 21-sulfate, [.alpha.]D 90-5.degree. (1% in H2O), .lambda. 238, E1%1cm. 291; testosterone propionate, m. 117-22.degree.; N-acetylpenicillamine ethyl ester, m. 91-8.degree.; methandriol diacetate, m. 145-7.degree.; ethyl ester of cholic acid diacetate, m. 183.degree. (decompn.); ethyl phenaceturate, m. 88-90.degree.; estradiol benzoate, m. 227-9.degree.