Process for the preparation of penicillanic acid esters
AssigneePfizer Inc.
InventorVytautas J. Jasys
Life of this patent
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Abstract
A process for the preparation of chloromethyl esters of penicillanic acids, using iodochloromethane or bromochloromethane and a tetraalkylammonium salt of the penicillanic acid, and their use in processes for the synthesis of penicillanic acid esters, using a halomethyl ester and the tetraalkylammonium salt of the penicillanic acid, which readily hydrolyze in vivo to antibacterial penicillins and the beta-lactamase inhibitor penicillanic acid sulfone.
Claims20
A process for the preparation of a compound selected from those of the formula ##STR23## wherein n is an integer of 0 or 2, R is selected from the group consisting of
- (a) hydrogen, ##STR24## wherein R.sub.2 is selected from the group consisting of hydrogen and hydroxy and R.sub.1 is selected from the group consisting of azido, amino, carbobenzyloxyamino and 1-methoxycarbonylpropen-2-ylamino, which comprises contacting one mole of a compound of the formula ##STR25## wherein R.sub.3 is alkyl having from one to four carbon atoms, with at least one mole of a solvent selected from the group consisting of bromochloromethane and iodochloromethane at from about -20.degree. C. to about 25.degree. C. with the proviso that when n is 2, R is hydrogen.
A process for the preparation of a compound selected from those of the formula ##STR27## wherein X is selected from the group consisting of ##STR28## wherein R.sub.1 is selected from the group consisting of azido, amino, carbobenzyloxyamino and 1-methylcarbonylpropen-2-ylamino and R.sub.2 is selected from the group consisting of hydrogen and hydroxy, which comprises contacting one mole of a compound selected from those of the formula ##STR29## wherein Y is selected from the group consisting of chloro, bromo and iodo, with at least one mole of a compound selected from those of the formula ##STR30## wherein R.sub.3 is alkyl having from one to four carbon atoms in a reaction-inert solvent at ambient temperatures.
A process for the preparation of a compound selected from those of the formula ##STR32## wherein X is selected from the group consisting of ##STR33## wherein R.sub.1 is selected from the group consisting of azido, amino, carbobenzyloxyamino, and 1-methoxycarbonylpropen-2-ylamino and R.sub.2 is selected from the group consisting of hydrogen and hydroxy, which comprises contacting one mole of a compound selected from those of the formula ##STR34## with at least one mole of a compound selected from those of the formula ##STR35## wherein R.sub.3 is alkyl having from one to four carbon atoms and Y is selected from the group consisting of chloro, bromo and iodo, in a reaction-inert solvent at from about 0.degree. to about 60.degree. C.
Dependencies are inferred from the claim text.