{"created":"2023-05-15T15:03:54.002944+00:00","id":86453,"links":{},"metadata":{"_buckets":{"deposit":"72e001e5-d235-4da8-9820-8eabf7269bde"},"_deposit":{"created_by":1,"id":"86453","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"86453"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00086453","sets":["2"]},"author_link":["1055381","1055387","1055386","1055385","1055390","1055391","1055389","1055383","1055382","1055384","1055392","1055388"],"item_10003_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2022-06","bibliographicIssueDateType":"Issued"},"bibliographic_titles":[{"bibliographic_title":"Nuclear Medicine and Biology"}]}]},"item_10003_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Objectives: The trifluoromethyl group can improve physicochemical properties, such as metabolic stability, lipophilicity and pharmacokinetics of targeted probes. Radiolabeling by trifluoromethyl group is an attractive method to synthesize a useful PET probe. Recently, Haskali et al. have developed the synthetic method of [11C]fluoroform from [11C]CH4 with a CoF3 column and the application route of [11C]fluoroform for various trifluoromethylation reactions [1]. However, those application reactions were not automated and the synthesis of [11C]CF3-aryl derivatives is difficult because preparation of [11C]CuCF3 as a trifluoromethylation reagent was conducted in a glove box to avoid air and moisture. Herein, we developed a synthetic method of [11C]CF3-aryl derivatives using a fully-automated system equipped with [11C]CuCF3 without glove box.\nMethods: [11C]Trifluoromethylation of aryl precursor was performed by using a fully-automated synthesis system (Scheme 1). [11C]Fluoroform was produced by passing [11C]CH4 through a column that was precoated with cobalt(III) fluoride (24 g) and heated at 350 oC. CuOtBu was generated by mixing t-BuOK (15 mol) with CuBr (5 mol) in DMF (0.3 mL) in a sealed vial under N2. Preparation of [11C]CuCF3 was performed by bubbling [11C]fluoroform into the CuOtBu solution at -45 oC. After the radioactivity of [11C]fluoroform reached a plateau, the reaction mixture was warmed to room temperature for 2 min and then added Et3N-3HF (0.82 L) in DMF (0.2 mL). The trifluoromethylation was performed by the reaction of [11C]CuCF3 with aryl precursor (10 mg) at room temperature or 130 oC for 5 min. After the preparative HPLC mobile phase (1.0 mL) was added, the reaction mixture was applied to the HPLC system for separation. The HPLC fraction of [11C]1 was directly collected in a vial. The radioactive product was analyzed by HPLC with radioactivity and UV-VIS detectors. \n\n \nScheme 1. Preparation of [11C]CuCF3 and synthesis of [11C]CF3-aryl derivatives\n\nResults: We prepared CuOtBu without a glove box by carefully treating the all reaction reagents under N2. Reaction of aryl precursor and [11C]CuCF3 did not proceed because HF that was produced by the decomposition of CoF3 prevented the [11C]trifluoromethylation reaction. To solve this problem, we tested various Sep-Pak cartridges to trap HF. Of them, silica plus Sep-Pak cartridge completely removed HF. When using aryl boronic acid as a precursor, [11C]1 was synthesized in 3 ± 1% (n = 5) radiochemical yield from [11C]CH4 at the end of irradiation, with > 99% radiochemical purity. The average total synthesis time from the end of bombardment was 35 min.. On the other hand, when using aryl iodide as a precursor, [11C]1 was only obtained in trace amount. The application scope of [11C]trifluoromethylation is under investigation.\n\nConclusions: We succeeded in the [11C]trifluoromethylation of aryl precursors with [11C]CuCF3 using a full-automated system.  We are currently optimizing reaction conditions to improve the radiochemical yield of [11C]1.\nAcknowledgements: This research is supported by QST President’s Strategic Grant Exploratory Research.\n","subitem_description_type":"Abstract"}]},"item_10003_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Elsevier Ltd."}]},"item_10003_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0969-8051","subitem_source_identifier_type":"ISSN"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"metadata only access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_14cb"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Masayuki, Fujinaga"}],"nameIdentifiers":[{"nameIdentifier":"1055381","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Masanao, Ogawa"}],"nameIdentifiers":[{"nameIdentifier":"1055382","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nobuki, Nengaki"}],"nameIdentifiers":[{"nameIdentifier":"1055383","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Katsushi, Kumata"}],"nameIdentifiers":[{"nameIdentifier":"1055384","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Wakana, Mori"}],"nameIdentifiers":[{"nameIdentifier":"1055385","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Ming-Rong"}],"nameIdentifiers":[{"nameIdentifier":"1055386","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Masayuki, Fujinaga","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1055387","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Masanao, Ogawa","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1055388","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nobuki, Nengaki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1055389","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Katsushi, Kumata","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1055390","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Wakana, Mori","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1055391","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Ming-Rong","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1055392","nameIdentifierScheme":"WEKO"}]}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"conference paper","resourceuri":"http://purl.org/coar/resource_type/c_5794"}]},"item_title":"The fully-automated synthesis of [11C]CF3-aryl derivatives with [11C]fluoroform","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"The fully-automated synthesis of [11C]CF3-aryl derivatives with [11C]fluoroform"}]},"item_type_id":"10003","owner":"1","path":["2"],"pubdate":{"attribute_name":"公開日","attribute_value":"2022-05-06"},"publish_date":"2022-05-06","publish_status":"0","recid":"86453","relation_version_is_last":true,"title":["The fully-automated synthesis of [11C]CF3-aryl derivatives with [11C]fluoroform"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T16:57:42.377961+00:00"}