CH307628A - Process for the preparation of the hydrochloride of D-threo-1-p-nitrophenyl-1-dichloroacetoxy-2-amino-3-oxypropane. - Google Patents

Description

  

  Process for the preparation of the hydrochloride of D-threo-1-p-nitrophenyl-1-dichloroacetoxy-2-amino-3-oxypropane. 1: It was found that by treating D-threo-2-dichloromethyl-4-oxy-iilethyl-5-p-nitrophenyloxazoline (formula I)
EMI0001.0010
    with mineral acids, preferably hydrochloric acid 5t.offsä-uire,

      D-threo-1-p-nitrophenyl-1-diehloracetoxy-2-amino-3-oxypropane (Formula 1I) salts which can easily be converted into chloramphenieneol.



  The subject of the present patent is a process for the preparation of the hydrochloride of D-threo-lp-nitrophenyl-l-dichloro-aeetoxy - 2 - amino - 3 - oxypropane, which is characterized by the fact that D-threo- 2- Diehlormet.hy 1- 4 - oxymethyl - 5 -p-nitrophenyl- oxazoline treated with hydrochloric acid in the presence of a moist organic solvent,

   which contains less water than would be necessary to dissolve the hydrochloride formed, so that the latter separates out in the reaction mixture. Most often the hydrochloride separates out in the form of an oil; the reaction mixture is then advantageously concentrated and the oily syrup obtained is treated with ether to crystallize the hydrochloride.



  The hydrochloride of D-threo-1-p-nitrophenyl -1-dichloroacetoxy-2-amino-3-oxypropane obtained in this way is a new, colorless, crystallized substance which melts at 150 to 154 and which is used as an intermediate product for the production of chloramphenicol can be.



  For a quantitative conversion, 1 mole of water is required for 1 mole of starting material. In general, it is sufficient to use non-dried, that is, moist organic solvents such as acetone, alcohol, etc., and possibly the simultaneous use of concentrated aqueous hydrochloric acid in order to obtain the required amount of water.



  The D-threo-2-dichloromethyl - 4 - oxyineth @ rl - 5 - p-nitrophenyl oxazoline required as starting material can be obtained by acylating DL-threo-ss-phenylserine on nitrogen, producing the quinine salt from the acylation product and fractionally crystallized, the less soluble component splits with alkali into L-threo-N-acetyl-ss-phenylserine, then entacylated to L-threo-ss-phenylserine and esterified,

   the L-threo-ss-Plieziylserin- ester diaeylated, this acylation product nitrated, then hydrolyzed to L-threo-ss, p-nitropheny 1-serine, esterified again, the L-threo-ss,

  p-Nitrophenylserine ester with dichloroacetimido-alkyl ether to L-threo-2-dichloromethyl - 4-earbalkoxy - 5-p-nitrophenyloxazoline and the latter with lithium borohydride to D-threo? -Dichloromethyl-4-oxymethyl- 5-p-nitrophenyl-oxazoline reduced.



  The hydrochloride of D-threo-1-p-nitrophenyl-1-diehloracetoxi> - 2-amino-3-oxy propane is easily soluble in water and can be converted into chloramphenicol by adding alkali to the aqueous solution. Example <I> Z: </I> 5 parts by weight of D-threo-2-dichloromethyl-4-oxymethy1-5-p-nitrophenyl-oxazoline are dissolved in 30 parts by weight of anhydrous acetone.

    Then 10 parts by weight of 30% alcoholic hydrochloric acid (96% alcohol) are added so that the solvent mixture (alcohol-acetone) contains 1 lo water. After a while, the desired hydrochloride separates out in an oily form. The seeded reaction mixture is concentrated in a water jet vacuum at room temperature, an oily syrup being obtained.

   After adding absolute ether in excess, the D - threo -1 -p -nitrophenyl-1-dicliloroacetoxy-2-amino-3-oxypropane hydrochloride separates from the melting point 150-154 in crystalline form. The yield is 4.5 parts by weight.

           Example <I>; 3: </I> 5 (percentages of D-tlireo-2-dichloromiethyl-4-oxymethyl-5-p-nitroplieiivl-oxazoline are dissolved in a little moist alcohol, then concentrated hydrochloric acid is added until a congo acidic reaction occurs and cooled, whereupon the D-thr eo -1- p - nitroplienyl-1-dichloroacetoxy - 2 - amino-3-oxypropane hydrochloride separates in solid form, the yield is 3.6 parts by weight.

 

Claims (1)

PATENT CLAIM Process for the production of the hydrochloride of D-threo-l-p-nitrophenyl-l-diehloracetoxy-2-amino-3-oxypropane. characterized in that D-threo - \ _'- Diehlor- methy 1- 4 - oxymethy l - 5-p-nitroplieny 1-oxazoline treated with hydrogen chloride in the presence of a moist organic solvent, which contains less water, than would be necessary to dissolve the hydrochloride formed, so that the latter separates out in the reaction mixture. The new salt thus obtained is a colorless, crystallized substance which melts at 150-154. TUT N TER CLAIM Process according to Patetitanspriteli, characterized in that the reaction mixture, which contains the deposited hydrochloric acid in the form of an oil, is treated with ether and the oily syrup obtained is treated with ether in order to crystallize the hydrochloride.