Process for preparing cyclophosphamide, intermediates, and monohydrate thereof

A process for preparing cyclophosphamide monohydrate, comprising the steps of:

• (a) providing bis (2-chloroethyl) amine hydrochloride;
• (b) converting bis (2-chloroethyl) amine hydrochloride into cyclophosphamide monohydrate represented as formula I, and
• wherein the converting comprises the step of reacting bis (2-chloroethyl) amine hydrochloride with phosphorus oxychloride in the presence of a base in toluene at a temperature ranging from 20° C. to 60° C. to form bis-(2-chloroethyl)-phosphoramidic dichloride represented as formula II:
• wherein the bis-(2-chloroethyl)-phosphoramidic dichloride represented as formula II is converted into the cyclophosphamide represented as formula I by reacting with 3-amino-1-propanol in the presence of the base in a solvent and purifying and isolating to yield a crystalline of cyclophosphamide monohydrate represented as formula I.