Synthesis of carbon‐13 labeled 5‐(diethylphosphono)‐2‐pentanone ethylene ketal, a reagent for synthesis of multi C‐13 labeled steroids

Abstract Alkylation of ethyl acetoacetate‐ 13 C 4 with ethylene oxide and ethylene oxide‐ 13 C 2 afforded 2‐acetylbutyrolactone‐ 13 C 4 ( 4a ) and the hexalabeled form ( 4b ), respectively. Treatment of the lactone with an excess of 48% hydrobromic acid effected decarboxylation with bromide displacement to yield 5‐bromo‐2‐pentanone labeled with 3 or 5 carbon‐13 atoms ( 5 ). The bromo ketone was converted to the ethylene ketal with ethylene glycol and p ‐toluenesulfonic acid catalysis. Displacement of the bromide by sodio diethyl phosphite gave the required ethylene ketals of 5‐(diethylphosphono)‐2‐pentanone ( 7 ). A convenient process for preparation of ethylene‐ 13 C 2 oxide from acetic‐ 13 C 2 acid is also described.