摘要 |
<p>FIELD: chemical industry. SUBSTANCE: present invention describes process of asymmetric preparation of florphenycol of formula I: <EMI ID=0.376 HE=30 WI=54 TI=CHI>. Said process comprises the following stages: (1) stage of regioselective opening of chiral epoxide of formula II: <EMI ID=0.377 HE=27 WI=48 TI=CHI> by successive treatment with strong base, Lewis acid and dichloroacetonitrile to obtain oxazoline of formula III: <EMI ID=0.378 HE=30 WI=57 TI=CHI>; (2) stage of selective inversion/isomerization of the resulting oxazoline of formula III by successive treatment of tertiary amine and lower alkylsulphonyl chloride, aqueous acid and alkali metal hydroxide to obtain oxazoline of formula IV: <EMI ID=0.379 HE=36 WI=48 TI=CHI>; stage of treatment of oxazoline of formula IV with fluorination agent followed by acid hydrolysis. The present invention also describes method of regioselective opening of chiral epoxide of formula given above by successive treatment with strong acid, Lewis acid and dichloroacetonitrile to obtain oxazoline of formula III. The present invention also describes process of preparing R, S-florphenicol isomer of formula I given above which comprises isomerizing S,S-florphenycol of formula V: <EMI ID=0.380 HE=27 WI=51 TI=CHI> by successive treatment with tertiary amine and lower alkylsulfonyl chloride, aqueous acid and alkali metal hydroxide. EFFECT: more effective and efficient preparation of florphenicol. 4 cl, 2 dwg, 3 ex</p> |