GB699808A - Process for the epimerisation of diastereoisomeric amino diols - Google Patents

Abstract

Epimerization of erythro - 2 - acylamino - 1 - nitrophenylpropane - 1 : 3 - diols (optically active or racemic) is effected by forming a dinitric ester thereof, treating this with alkali to hydrolyse the 1-ester group with cyclization to an oxazoline, opening the oxazoline ring by the action of acid, treating the resulting propanol with alkali to hydrolyse the 3-ester group and again form an oxazoline ring, opening this by the action of acid and finally neutralizing the reaction mixture with a base. The acyl radical in the 2-acylamino substituent may be, for example, a lower aliphatic acyl radical (acetyl being mentioned in the Provisional Specification), a halogenated lower aliphatic acyl or a benzoyl radical. The formation of the dinitric ester of the erythro diol may be effected by treating this compound with nitric acid (s.g. 1.50) at about 0 DEG C. (not above 5 DEG C.), or by the method illustrated in example 1 below. The remaining stages are likewise preferably carried out in the cold, the alkali treatments advantageously in aqueous alcohol. In examples (1) the dinitric ester of DL-erythro-2-dichloracetylamino - 1 - o - nitrophenyl - 1 : 3 - diol is prepared by treating DL-erythro-5-di-chloracetylamino - 4 - phenyl - 2 - methyl - 1 : 3 - dioxan with nitric acid (s.g. 1.50) at a temperature rising from -40 DEG to 0 DEG C. and is treated with aqueous methanolic caustic soda, the resulting oxazoline is treated with concentrated hydrochloric acid, the last two steps are repeated and the final reaction mixture diluted and neutralized with solid sodium bicarbonate; (2) DL - erythro - 2 - dichloracetylamino - 1 - p - nitrophenylpropane - 1 : 3 - diol is treated with nitric acid (s.g. 1.50) at a temperature rising from -30 DEG to +10 DEG C., and the resulting dinitrate treated as in (1); the caustic soda in the first alkali treatment may be replaced by caustic potash, potassium carbonate or triethylamine and the sodium bicarbonate in the final neutralization by ammonia; (3) the DL-compound in (2) is replaced by the L-isomer, the final product being chloramphenicol; (4) the aqueous methanolic caustic soda in the second alkali treatment in (2) is replaced by aqueous caustic soda, and the product is further treated without isolation. Specification 692,265 is referred to. The Provisional Specification comprises generally the epimerization of compounds of the general formula <FORM:0699808/IV (b)/1> wherein R3 and R4 are the same or different and each represent a hydrogen or halogen atom or a lower alkyl or alkoxy radical, R5 represents hydrogen or a nitro group and R6 an acyl radical. Specification 673,864 also is referred to.