METHOD OF SYNTHESIS OF 2-[BIS-(2-CHLOROETHYL)AMINO]-TETRAHYDRO-2H-1,3,2-OXAZAPHOSPHORIN-2-OXIDE MONOHYDRATE Russian patent published in 2003 - IPC

FIELD: organic chemistry, chemical technology. SUBSTANCE: invention relates to organic synthesis, in particular, to method of synthesis of 2-[bis-(2-chloroethyl)amino] tetrahydro-2H-1,3,2-oxaza-phosphorin-2-oxide monohydrate used in pharmacy as an antitumor preparation cyclophosphan. By proposed method the end product is synthesized from diethanolamine by 3-staged schedule: at the first stage diethanolamine and thionyl chloride taken in the ratio = 1: (2.5-3.0) are boiled in chloroform medium and reaction product is isolated by acetone addition. Isolated product is boiled in phosphorus oxychloride medium and product is isolated by addition of carbon tetrachloride; isolated product is subjected for interaction with 3-aminopropanol at temperature 15-20 C; product of this stage is treated with water and obtained product is crystallized from ethyl acetate at temperature (-5) C - (-10) C. The proposed technology allows to the advanced yield of end product up to 49.4% as measured for the parent diethanolamine and obtain product corresponding to Pharmacopoeia requirement. EFFECT: improved method of synthesis, simplified technology, advanced yield. 1 cl, 1 ex