From [11C]CO2 to [11C]amides: a rapid one-pot synthesis via the Mitsunobu reaction† †Electronic supplementary information (ESI) available: Experimental details and NMR spectra. See DOI: 10.1039/c7cc01407d

Radiosynthesis of [11C]amides via the Mitsunobu reaction.

MHz spectrometer. Mass spectroscopy was performed using on an Agilent 6520 Accurate-Mass Q-TOF LC/MS connected to an Agilent 1200 HPLC system with UV detector and autosampler.

S2
General procedure for synthesis of 1C, 5C and 6C The corresponding amine (1, 5 or 6, 138.6 μmol, 1 equiv.) and DBU (1 µL, 6.9 μmol, 0.05 equiv.) were added in dry Et 2 O (1 mL) under nitrogen. The sealed vial was placed in an ice-bath and CO 2 was bubbled for 5 min at 0°C. The reaction mixture was stirred for 35 min at room temperature. To this solution was added a solution of DBAD (64.5 mg, 277 μmol, 2 equiv.) and Bu 3 P (70 µL, 277 μmol, 2 equiv.) in dry Et 2 O (0.5 mL) prepared under nitrogen and stirred for 10 min. The reaction mixture was stirred for additional 10 min before adding phenylmagnesium bromide (C, 1 mL, 1 mmol, 7.2 equiv.) at 0 °C under nitrogen. Then the reaction was warmed at room temperature and stirred 30 min before being quenched with oxalic acid (0.6 M, 2 mL). The organic phase was washed with brine (20 mL), dried over MgSO 4 , concentrated under reduced pressure and purified by flash column chromatography (silica gel, 100-70% hexane/EtOAc gradient). Grignard reagents, 1-propynylmagnesium bromide (0.5 M in THF) and methylmagnesium bromide (1:1) was used to quench the reaction. 1A and melatonin were used as reference compounds. [ 11 C]CO 2 was produced using a Siemens RDS112 cyclotron by the 11 MeV proton bombardment of nitrogen (+ 2% O 2 ) gas via the 14 N(p,α) 11 C reaction. The cyclotron-produced [ 11 C]CO 2 was bubbled in a stream of helium gas with a flow rate of 60 mL/min post target depressurisation directly into a reaction v-vial.

N-benzylbenzamide
HPLC analysis was performed on an Agilent 1200 system equipped with a UV detector (λ=254 nm) and a β + -flow detector coupled in series.

General Radiosynthetic procedure
An oven-dried vial (KX Microwave Vials, 5 mL) and a crimp cap (Fisherbrand, centre hole with 3.0 mm PTFE seal aluminum silver 20 mm, part # 10132712) were used. All gas transfer lines were An aliquote of the crude was injected in the radio-HPCL (C18 column, UV and radio detector) in order to determine the RCY. Analytical reverse-phase column (ZORBAX Eclipse XDB-C18, 4.6 x 150 mm, 5 μm) was used with a flow rate of 1 mL/min. The gradient was linear between 20-80% over 5 min mm, 5 µm) with a flow rate of 1.5 mL/min (70% water and 30% Acetonitrile, isocratic). The retention time of Melatonin is 9 minutes and 38 seconds. Radiochemical purity was assessed by injecting the radiotracer alone. Identity of the radiolabelled product was confirmed by co-injection with the unlabelled reference standard (see chromatograms below). seconds and is in the range of delay of this instrument (~20 seconds).

Fig. S2 A)
Radio-HPLC radiochromatogram of purified [ 11 C]Melatonin. B) UV-Chromatogram of purified [ 11 C]melatonin spiked with non-radioactive Melatonin. The difference between UV peaks (retention time (t R ) = 3 minutes and 58 seconds) and radioactivity peaks (t R = 4 minutes and 16 seconds) is 18 seconds and is in the range of delay of this instrument (~20 seconds).  Table 1.