10.1002/adsc.201901419
Advanced Synthesis & Catalysis
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generate a labeling agent from D2O. The principles
outlined herein, entailing conversion of carbonyl
containing drugs into enolates and its reaction with an
in situ generated electrophilic partner, provide a new
rational framework for late-stage modification of a
drug candidate. Studies along these lines are in
progress.
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Experimental Section
General Procedure for the Synthesis of 2a
To a 15 mL oven-dried pressure vessel was added
nabumetone 1a (0.2 mmol), B(C6F5)3 (10 mol%), THF (0.4
mL), and D2O (10 mmol). The reaction mixture was
allowed to stir for 12 hours at 100 °C. Upon completion,
the reaction mixture was concentrated in vacuo. After
purification by column chromatography (Et2O:hexanes =
1:9), 2a was obtained as a white solid (45 mg, >95% yield).
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1H NMR (500 MHz, CDCl3) δ 7.65 (d, J = 8.5 Hz, 2H),
7.53 (s, 1H), 7.27 (d, J = 8.4 Hz, 1H), 7.15 – 7.07 (m, 2H),
3.89 (d, J = 2.0 Hz, 3H), 3.00 (s, 2H), 2.83 – 2.74 (m,
0.10H, 95%D), 2.13 – 2.08 (m, 0.14H, 95%D); 13C NMR
(126 MHz, CDCl3) δ 208.22, 157.26, 157.21, 136.06,
133.06, 132.99, 129.03, 128.87, 128.86, 127.47, 126.92,
126.86, 126.19, 118.76, 105.62, 55.24, 44.58, 44.43, 44.29,
29.60, 29.55; IR (neat) 2931, 1703, 1633, 1604, 1484,
1461, 1391, 1246, 1232, 1161, 1030, 853, 817 cm-1;
HRMS (DART) Calcd for C15H12D5O2 (MH+): 234.1537;
found: 234.1547.
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Acknowledgements
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Financial support was provided by the NIH (GM-128695), the
Sloan Foundation, and Boston College.
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