Chlorotrimethylsilane → Ampicillin

Participants

Reaction Steps

Ampicillin triethylamine salt (2.7 g.) is suspended in 25 ml. tetrahydrofuran, cooled to 5°, 1.52 ml. of trimethylsilyl chloride is added and stirred for about 10 minutes followed by the addition of 3 ml. of triethylamine and the cooling bath removed for 30 minutes. Cooling is renewed and 1.8 g. of 6-[m-(1-pyrrolidinyl)phenyl]-1,2-dihydro- 2-oxonicotinyl chloride hydrochloride is added with the reaction media temperature being maintained at about 2°. The mixture is stirred for 3 hours at room temperature and then filtered. The solid is washed 3 times with 15 ml. tetrahydrofuran and the combined tetrahydrofuran solution is evaporated to dryness at 40° in vacuo. The residue is mixed with ice water, adjusted to pH 8.5-9.0 with sodium hydroxide solution, and filtered through filter aid being careful to keep the solution cold. The filtrate is acidified with 1N hydrochloric acid to pH 2.5, and the precipitate collected by filtration and partly dried. The product is dissolved in 50 ml. 2-butanone, and the solution is dried with sodium sulfate and filtered. The filtrate is mixed with 200 ml. of hexane to precipitate a dark brown solid. The solid is collected, air dried and extracted with 200 ml. of acetonitrile. The yellow extract is evaporated to dryness in vacuo to give N-[6-m-(1-pyrrolidinyl)-phenyl]-1,2-dihydro-2-oxonicotinyl]ampicillin (yield 0.19 g.), [α]D25 = 188° (0.233% in 3-1 N,N-dimethylformamidepyridine) λ = 342 E.function. = 189 (in pH 7 buffer containing 2.5% N,N-dimethylformamide) Assayed 111%, 113.6 penicillin G equivalents colorimetrically.

Provenance & Evidence