SYNTHETIC COMMUNICATIONS®
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1.46 (d, J ¼ 3.0 Hz, 9H). 13C NMR (101 MHz, CDCl3) δ 171.08, [170.63, 170.50], [169.67,
169.58], 144.60, 128.72, 127.97, 127.05, [82.70, 82.66], 70.68, [53.28, 52.97], 44.05, [33.56,
33.45], [28.57, 28.18], 28.01, 22.62. HRMS (ESI): m/z [MþH] calcd. for C31H35BrN2O4:
578.1780. Found: 578.1783.
(2S)-tert-Butyl 2-(2-fluoropropanamido)-5-oxo-5-(tritylamino)pentanoate 7
The 1M TBAF in THF (4 mL) was added dropwise to a solution of (2S)-tert-butyl 2-(2-
bromopropanamido)-5-oxo-5-(tritylamino)pentanoate 6 (1.16 g, 2 mmol) in dry CH3CN,
left to stir at 90 °C for 10 h, then the removal of solvent to afford an oil crude. The crude
product was purified by column chromatography on silica gel (petroleum ether/EtOAc ¼
2:5) to afford the title compounds as white solid 7 (0.40 g, 40%), mp 153 °C. 1H NMR (400
MHz, CDCl3) δ 7.31–7.18 (m, 16H), 7.06 (dd, J ¼ 14.3, 8.0 Hz, 2H), 4.96 (dp, J ¼ 49.2,
6.7 Hz, 1H), 4.45 (qd, J ¼ 9.1, 3.8 Hz, 1H), 2.47–2.17 (m, 3H), 1.98–1.84 (m, 1H), 1.56
(ddd, J ¼ 24.5, 6.7, 5.1 Hz, 3H), 1.46 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 171.21,
[171.08, 171.01], [170.88, 170.85, 170.59, 170.54], 144.69, 128.75, 127.95, 127.03, [89.41,
89.37, 87.58, 87.55], [82.72, 82.68], 70.67, [52.18, 52.06], [33.71, 33.63], [28.99, 28.84],
28.02, [18.77, 18.55, 18.44, 18.23]. 19F NMR (376 MHz, CDCl3) δ À 182.18 to À 182.58
(m). HRMS (ESI): m/z [MþH] calcd. for C31H35FN2O4: 518.2581. Found: 518.2575.
(2S)-5-Amino-2-(2-fluoropropanamido)-5-oxopentanoic acid 8
(2S)-tert-Butyl-2-(2-fluoropropanamido)-5-oxo-5-(tritylamino)pentanoate 7 (320 mg, 0.62
mmol) was added to a mixed solution of trifluoroacetic acid (20 mL) and dichloromethane
(2 mL). The resulting mixture was stirred overnight at room temperature. After the
removal of solvent under vacuum to give the residue, 1 M lithium hydroxide solution
(30 mL) was added and extracted with diethylether (3 � 20 mL). The aqueous phase was
made acidic with 1N hydrochloric acid to pH ¼ 4, extracted with ethyl acetate (3 � 40 mL),
combined the organic phase, and washed with water 40 mL, brine 40 mL, dried over
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Na2SO4, evaporated the solvent to afford yellow oil 8 (96 mg, 70%). H NMR (400 MHz,
CD3OD) δ 7.21–7.06 (m, 1H), 5.04–4.93 (m, 1H), 4.41–4.28 (m, 1H), 2.27 (dt, J ¼ 30.7,
7.2 Hz, 2H), 2.19–2.07 (m, 1H), 1.99–1.86 (m, 1H), 1.49–1.38 (m, 3H). 13C NMR (101
MHz, CD3OD) δ 176.43, 174.57, [173.65, 173.60, 173.44, 173.40], [90.17, 88.36], [52.80,
52.77], [31.26, 31.23], [27.62, 27.56], [19.01, 18.91, 18.79, 18.69]. 19F NMR (565 MHz,
CD3OD) δ À 184.36 to À 184.63 (m). HRMS (ESI): m/z [MþH] calcd. for C8H13FN2O4:
220.0859. Found: 220.0865.
(2S)-5-Amino-2-(2-[18F]fluoropropanamido)-5-oxopentanoic acid 10
[18F]Fluoride was trapped on QMA cartridge and eluted by K2CO3 (3 mg in 0.1 mL H2O)
and K2.2.2 (13 mg in 0.9 mL CH3CN) complex solution. [K/K2.2.2]
þ18FÀ elution was evapo-
rated under a nitrogen flow and completely remove the solvent at 95 °C under vacuum. A
mixture of precursor 6 (5–10 mg) in 1 mL anhydrous CH3CN was added to the reactor.
18F-fluorination reaction was performed at 110 °C for 15 min. The reaction mixture was
cooled, diluted with water (10 mL), passed through a preconditioned a Sep-Pak C18 plus
cartridge, and washed with water (5 mL). The 18F-labeled intermediate 9 was eluted with