METHOD OF PRODUCTION OF N,N-BIS(2-CHLOROETHYL)TETRAHYDRO-2H-1,3,2-OXAZAPHOSPHORINE-2-AMINE 2-OXIDE

摘要

The invention relates to a method of production of N,N-bis(2-chloroethyl)amino)-2-oxo-1,3,2-oxazaphosphorinane in a reaction of phosphorous oxychloride POCl₃, N,N-bis(2-chloroethyl)amine, and 3-aminopropan-1-ol in a single reaction vessel, characterized by the fact that phosphorous oxychloride and N,N-bis(2-chloroethyl)amine hydrochloride are added to an inert aprotic organic solvent placed in a closed reaction vessel, in a slight molar excess in relation to phosphorous oxychloride, whereupon the mixture is cooled to temperature in the range of −15 to −10° C., and with the temperature maintained within this range and continuous stirring, the solution of 3-aminopropan-1-ol and the first portion of the auxiliary base is slowly added in an amount of 1 mole calculated as per 1 mole of 3-aminopropan-1-ol in an inert aprotic organic solvent, and subsequently, while maintaining the reaction mixture temperature in the range of −7 to −3° C. the second portion of the auxiliary base is added dropwise, in an amount required for binding of HCl released during the cyclisation reaction, and after the mixture reaches temperature in the range of 15 to 20° C. it is stirred in this temperature for a period of 5 to 25 hours, whereupon, while continuously stirring, the remaining portion of the auxiliary base is added dropwise, in an amount of 2-2.3 moles, calculated per a theoretical amount of hydrochloride released from bis(2-chloroethyl)amine hydrochloride and released in the reaction of substitution of chlorine at the phosphorous atom in 2-chloro-tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide, and without stopping the stirring, the temperature is gradually increased from 20 to 40° C., the reaction being conducted until the conversion of the substrates is complete.