Synthesis of ¹⁵N labelled isophosphoramide mustard

The ifosfamide metabolite isophosphoramide mustard (IPM) was synthesized with isotopic enrichment at each nitrogen site. Glycine‐ 15 N was converted to 2‐chloroethylamine‐ 15 N hydrochloride (4 steps, 21% net yield) which was then reacted with phenyl dichlorophosphate to provide N,N ′‐bis(2‐chloroethyl)phosphorodiamidic‐ 15 N 2 acid phenyl ester [62%, PhOP( O ) ( 15 NHCH 2 CH 2 Cl) 2 ]. Catalytic hydrogenation of this phenyl ester followed by the addition of cyclohexylamine (CHA) provided IPM‐ 15 N 2 as the CHA salt (63%).