• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Scientific Publications by FDA Staff

  • Print
  • Share
  • E-mail

Search Publications



Starting Date

Ending Date

Order by

Entry Details

J Labelled Compd Rad 1995 Dec;36(12):1193-8

Synthesis of cyclophosphamide-4,4,5,5-d4

Walsh SP, Shulman-Roskes EM, Anderson LW, Chang YH, Ludeman SM


3-Hydroxypropionitrile was subjected to a base-catalyzed exchange reaction in D2O which provided 2,2-dideuterio-3-deuteroxypropionitrile (DOCH2CD2CN) in 70% yield. Reduction of the nitrile with LiAlD4 gave 3-amino-2,2,3,3-tetradeuteriopropan-1-o1 (HOCH2CD2CD2NH2) in a crude yield of 71%. Reaction of this intermediate with N,N-bis(2-chloroethyl)phosphoramidic dichloride [Cl2P(O)N(CH2CH2Cl)2] followed by the combination of those chromatography fractions which contained only pure material gave cyclophosphamide-4,4,5,5-d4 as a white oil in 13% yield. A portion of this oil was converted to the monohydrate by the addition of water (1.1 equivalents) and crystallization from ether/petroleum ether (62% yield). For the hydrate, MS analyses gave an average mole percent enrichment (with average deviation over 5 determinations) of 89.1 ± 0.5% d4.

Category: Journal Article
DOI: 10.1002/jlcr.2580361209
Includes FDA Authors from Scientific Area(s): Drugs
Entry Created: 2012-12-25