@misc{oai:repo.qst.go.jp:00071713,
 author = {Fujinaga, Masayuki and Ogawa, Masanao and Kumata, Katsushi and Shimoda, Yoko and Kawamura, Kazunori and Zhang, Ming-Rong and 藤永 雅之 and 小川 政直 and 熊田 勝志 and 下田 陽子 and 河村 和紀 and 張 明栄},
 month = {May},
 note = {Objectives: [11C]Phosgene ([11C]COCl2) is an important 11C-labeling reagent for synthesizing various radioactive
compounds containing a [11C]urea or [11C]carbamate moiety. We have developed several 11C-labeled lignads
containing carbamate or unsymmetrical urea moiety using [11C]COCl2 and reported the synthesis of [11C]1 as a
novel PET ligand for imaging of fatty acid amide hydrolase using [11C]COCl2 or [11C]CO2 [1]. However, the synthesis
of [11C]1 had some problems in poor reactivity and reproducibility. In this study, we developed a method for
synthesizing [11C]1-3 via 2 routes, starting from several phenol derivatives and base, to improve the reproducibility
and versatility for constructing the [11C]carbamate moiety.
Methods: The alkylamine 10 was prepared from commercialy available materials. [11C]1-3 were synthesized by
reaction of phenol derivatives with [11C]COCl2 in the presence of various bases, followed by reaction with amine 10,
via 2 routes as shown in Scheme 1.
Results: In the case of route A, when Et3N, DMAP, pyridine, or DBU was used, [11C]1 was obtained with moderate
yield but [11C]2 or [11C]3 could not be obtained because 8 or 9 was formed at low yields. Instead of these bases,
when 1,2,2,6,6-pentamethylpiperidine was used, 7-9 were produced in 68%, 88%, and 91% yields, which were
determined by analyzing the reaction mixtures using radio-HPLC. However, following reaction of 8 or 9 with 10 did not
proceed. In the case of route B, when 1,2,2,6,6-pentamethylpiperidine was used, after [11C]COCl2 was trapped to the
reaction mixture, immediate addition of amine 10 to the mixture accomplished the reaction. After the two-steps
reaction, it was found that [11C]1-3 were produced with 92%, 82%, and 68% yields in the mixtures.
Conclusions: We succeeded in improvement of reaction efficiency of [11C]1-3. These results showed that utilization of
1,2,2,6,6-pentamethylpiperadine was more effective for constructing the [11C]carbamate moiety compared to other
bases, such as Et3N, DBU, and DMAP.
References: [1] Fujinaga M, et al. (2013) J Label Compd Radiopharm, 56, S92. [2] Kumata K, et al. (2015) ACS
Chemical Neuroscience., 21st International Symposium on Radiopharmaceutical Sciences},
 title = {「Development of efficient construction of [11C]carbamate moiety using [11C] COCl2」},
 year = {2015}
}