A simple synthesis of [11C]carfentanil using an extraction disk instead of HPLC

https://doi.org/10.1016/S0969-8051(01)00226-8Get rights and content

Abstract

[11C]Carfentanil was prepared without the need for purification by HPLC. The tetrabutylammonium salt of the precursor carboxylate was reacted with [11C]methyl triflate in DMSO. The resulting [11C]carfentanil was trapped on an Empore extraction disk and washed to remove precursor and most radioactive contaminants. The product was eluted by a small volume of ethanol, mixed with water and passed through a small column containing fibrous anion exchanger to remove remaining radioactive contaminants.

Introduction

The μ-opioid receptor agonist, carfentanil, is reported to have a potency 7000 times that of morphine [4]. In order to avoid pharmacological effects from [11C]carfentanil in human subjects the introduction of extraneous carbon-12 from all sources must be avoided during the synthesis. In addition, shortening the synthesis time significantly can further improve the specific activity. In the original synthesis of [11C]carfentanil reported by Dannals et al. (1985) the sodium salt of the carboxylate precursor was heated with [11C]methyl iodide to yield the desired methyl ester [2]. The latter was purified by HPLC. These time-consuming steps were avoided in the new synthesis reported below. The carboxylate precursor as the tetrabutylammonium salt was reacted at room temperature with [11C]methyl triflate. The product was trapped on a high performance extraction disk, and starting materials were selectively washed off. [11C]Carfentanil was eluted with a small volume of ethanol into water. Radioactive contaminants were further removed by a small column of fibrous anion exchanger. The synthesis was completed within five minutes after the distillation of the [11C]methyl triflate thus saving approximately one half-life.

Section snippets

Precursor

4-[N-(1-oxopropyl)-N-phenylamino]-1-(2-phenylethyl)-4-piperidinecarboxylic acid was obtained as the free amino acid as follows: Benzyl 4-[N-(1-oxopropyl)-N-phenylamino]-1-(2-phenylethyl)-4-piperidinecarboxylate hydrochloride [4] was hydrogenated (2 atm, 24 h) in ethanol in the presence of Pd/carbon (Aldrich 20,569–9). After removal of the solvent the residue was treated with excess aqueous NH4OH. The solution was evaporated to dryness. The resulting solid was taken up in a small amount of

Results and discussion

The purification and formulation of [11C]carfentanil were completed in five minutes after introduction of [11C]methyl triflate. Approximately 250 mCi [11C]carfentanil were obtained from 1600 mCi [11C]CO2. The average specific activity at end of synthesis was 3500 mCi/μmole. The radiochemical purity was 97–98%. The radioactive contaminants eluted before [11C]carfentanil in reversed phase HPLC. Residual precursor was detectable by reversed phase HPLC at low levels (approx. 0.1 ug/mL) in most

Acknowledgements

This research was supported by grants from the Department of Energy (DE-FG02-87ER60561) and from the Pritzker Foundation. The author received important advice from Bob Dannals and Marcian Van Dort.

References (5)

There are more references available in the full text version of this article.

Cited by (0)

View full text