Eli Lilly and Company

Ian G Wright

Wayne A Spitzer

Norbert Neuss

John Allan Rieck, Iii

Cis .alpha.,.alpha./.beta., .beta.-3-amino-4-[2-(2-furyl)eth-1-yl]-1-methoxycarbonylmethyl-azetidin-2- one is resolved via (-)-2,3:4,6-di-O-isopropylidene-2-keto-L-gulonic acid hydrate (DAG).

Method of resolving cis

Cis .alpha..alpha./.beta..beta.-3-amino-[2-(2-furyl)eth-1-yl]-1-methoxycarbony lmethyl-azetidin-2-one is resolved via optically active tartaric acid.

A process for preparing a C.sub.3 -C.sub.8 alkyl cyanoformate derivative employing a liquid-liquid phase transfer catalysis conducted at low temperatures.

Process for preparing cephalosporin intermediates

The silylated and enamine protected D-3- or 4-hydroxyphenylglycine as the sodium salt of the formula ##STR1## wherein A is methyl or ethyl, are crystalline intermediates useful in a new process for the acylation of heterocyclicthiomethyl-substituted cephalosporin nuclei, e.g. 7-amino-3-(5-methyl-1,3,4-thiadiazole-2-ylthiomethyl)-3-cephem-4-carboxyli c acid and 7-amino-3-(1-methyl-1H-tetrazole-5-ylthiomethyl)-3-cephem-4-carboxylic acid.

Process for preparing cephalosporin antibiotics

N,N'-Dichlorobicyclo[2.2.2]oct-7-ene-2,3,5,6-tetracarboxylic-2,3,5,6-diimid e is useful as a reagent in reactions which require a source of positive chlorine.

N,N'-dichlorobicyclo[2.2.2]oct-7-ene-2,3,5,6

The silylated and enamine protected D-3- or 4-hydroxyphenylglycine as the sodium salt of the formula ##STR1## wherein A is methyl or ethyl, are crystalline intermediates useful in a new process for the acylation of heterocyclic-thiomethyl-substituted cephalosporin nuclei, e.g. 7-amino-3-(5-methyl-1,3,4-thiadiazole-2-ylthiomethyl)-3-cephem-4-carboxyli c acid and 7-amino-3-(1-methyl-1H-tetrazole-5-ylthiomethyl)-3-cephem-4-carboxylic acid.

Process and intermediates for preparing cephalosporin antibiotics

4-Desacetoxy-4-oxovinblastine, prepared by oxidation of 4-desacetylvinblastine, useful as an intermediate.

4-Desacetoxy-4-oxovinblastine

A 3-methoxymethylcephalosporin acid is prepared by reacting a 3-hydroxymethylcephalosporin acid with a reagent selected from the group consisting of trifluoroacetic anhydride, phosphorus trichloride, phosphorus oxychloride, and thionyl chloride, and reacting the resulting intermediate with methanol.

Preparation of 3-methoxymethylcephalosporins

6-APA, 7-ACA and 7-ADCA esters are reacted with benzaldehyde, acetophenone or substituted derivatives thereof providing imines which react in the presence of a strong base such as sodium hydride or lithium diisopropyl amide with a C.sub.2 -C.sub.5 alkanoyl halide, 2,2,2-trichloroethoxycarbonyl chloride, a benzoyl halide, a C.sub.1 -C.sub.4 alkoxycarbonyl chloride or a methoxymethyl halide to afford C.sub.6 and C.sub.7 substituted .beta.-lactam imines via acylation or methoxymethylation. The .beta.-lactam substituted imines are reacted with a carbonyl reagent, e.g. Girard's reagent T to provide a C.sub.6 substituted 6-APA ester or a C.sub.7 substituted 7-ACA or 7-ADCA ester which is acylated to provide a 6-acylamido-6-substituted penicillin or a 7-acyl-amide-7-substituted cephalosporin.

7-Carboxy or 2,2,2-trichloroethoxy carbonyl- cephalosporins

This invention is addressed to a new and improved method for the preparation of 3-alkylthiomethyl-7-acylamido cephalosporins in which a 3-alkanoyloxymethyl-7-acylamido cephalosporin is reacted with an alkane thiol in aqueous medium in the presence of certain inorganic salts to produce the desired 3-alkylthiomethyl product in significantly improved yields.

Growing community of inventors

Greenwood, IN, United States of America

Ian G Wright