The Journal of Organic Chemistry
Note
was then passed through a column (25 mm x 15 cm) of a strong anion
exchange (SAX) resin eluted with a gradient method (0−10 min, 0−
60%; 10−15 min, 60%; 15−25 min, 60−100%) of 0.5 M
triethylammonium bicarbonate (TEAB) buffer pH 7.0 with a flow
rate of 8.0 mL/min (Figure S1). To eliminate minor impurity (19F
NMR, δ near −216.9 ppm), a modified14,15 gradient method (0−20
min, 0%; 20−35 min, 60−100%; 35−45 min, 100%) of 0.5 M TEAB
buffer pH 7.0 with a flow rate of 8.0 mL/min was used with the SAX
resin column. The desired compound eluted at 30.0 min (UV
detection at 259 nm; HPLC trace and 19F NMR spectra, Figure S19).
The fractions containing it were evaporated to yield the product as a
TEAH+ salt. 19F and 31P NMR analysis revealed traces of 2 in the
purified product.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by funding from the Dana and David
Dornsife College of the University of Southern California and
the National Institutes of Health (U19CA177547, C.E.M.) and
in part by a National Science Foundation Graduate Research
Fellowship (DGE-0937362, C.S.H.). We thank Inah Kang for
assistance in preparing the manuscript.
The product was next dissolved in 2 mL of 0.1 M TEAB (pH 7.0)
and purified on a C18 reversed-phase (RP-C18) preparative column (5
μm, 250 mm × 21 mm) by isocratic elution with 3.75% CH3CN in 0.1
M TEAB pH 7.0 at a flow rate of 8.0 mL/min. The product 1 eluted at
18.7 min (Figure S2). Evaporation of the corresponding collected
fractions gave 6.3 mg (7.8 μmol by UV, 20%) of a clear film as a
TEAH+ salt. ESI-MS: m/z 499 [M − H]−. 1H NMR (500 MHz, D2O,
pH 7.6, Figure S8) δ 7.99 (d, J = 8.2 Hz, 1H), 6.01 (t, J = 6.5 Hz, 2H),
4.53−4.35 (m, 2H), 4.31 (s, 1H), 4.26 (s, 2H). 19F NMR (470 MHz,
D2O, pH 10.4, Figure S9) δ −216.91 and −216.96 (ddd, J = 67.5, 54.6,
45.0 Hz, Δδ 24.0 Hz). 31P NMR (202 MHz, D2O, pH 10.4, Figure
S10) δ 7.46 (dd, J = 55.6, 14.3 Hz), 5.26 (ddd, J = 65.4, 28.3, 14.3 Hz),
−10.55 (d, J = 28.7, ΔδPα 4.0 Hz).
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1
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Immediately after NMR acquisition, the pH of the NMR sample
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ASSOCIATED CONTENT
■
S
* Supporting Information
HPLC analysis and preparative traces, counterion experimental
1
data, H NMR spectrum and additional 19F, 31P NMR spectra,
MS and UV−vis spectra for 1. This material is available free of
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AUTHOR INFORMATION
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Corresponding Author
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dx.doi.org/10.1021/jo500452b | J. Org. Chem. 2014, 79, 5315−5319