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centrated. The residual oil was loaded on a silica gel col-
umn and eluted with ethyl acetate to afford 200 mg of the
corresponding aniline (19% yield). 1H NMR (400 MHz,
CDCl3, ppm) d: 9.75 (1H, s), 7.72 (2H, d, J = 8.7 Hz),
6.66 (2H, d, J = 8.7 Hz), 4.80 (1H, s), 3.80 (2H, s), 3.78–
3.72 (2H, m), 3.69–3.57 (2H, m), 3.44 (2H, q, J = 5.3 Hz),
2.01 (1H, s). 13C NMR (100 MHz, CDCl3, ppm) d: 190.56
(CH), 153.45 (C), 132.54 (CH), 126.90 (C), 112.19 (CH),
72.49 (CH2), 69.44 (CH2), 62.01 (CH2), 43.04 (CH2). MS
(positive ESI, M + 1) m/z 210.3; (negative ESI, M – 1) m/z
208.3.
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4-Formyl-N-[2-(2-hydroxyethoxy)ethyl]benzamide
4-Carboxybenzaldehyde (1.015 g, 6.76 mmol) was dis-
solved in 16 mL of toluene. Once the aldehyde was dissolved,
p-toluenesulfonic acid (38 mg, 0.20 mmol) and ethylene gly-
col (415 µL, 7.44 mmol) was added. The reaction was re-
fluxed with a Dean–Stark apparatus overnight. Once the
reaction was complete, the toluene was evaporated and the re-
sidual oil was dissolved in ethyl acetate (30 mL) and washed
once with water (30 mL) and once with brine solution
(30 mL). The organic phase was collected, dried over
Na2SO4, and concentrated. The protected acid was recrystal-
lized from hexanes – ethyl acetate to afford 1.22 g of 4-
[1,3]dioxolan-2-yl-benzoic acid (92% yield). 1H NMR
(400 MHz, CDCl3, ppm) d: 8.02 (2H, d, J = 8.0 Hz), 7.49
(2H, d, J = 8.4 Hz), 5.78 (1H, s), 3.99 (4H, m). 4-[1,3]Dioxolan-
2-yl-benzoic acid (123 mg, 0.633 mmol) was dissolved
in 5 mL of DMF. Once the acid was dissolved, 2-(2-
aminoethoxy)ethanol (7 µL, 0.697 mmol) was added along
with DCC (196 mg, 0.950 mmol) and HOBt (128 mg,
0.950 mmol) and the reaction was allowed to stir at room
temperature overnight. Once the reaction was complete, the
mixture was dissolved in 10% sulfuric acid (5 mL) and left
to stir at room temperature for 2 h to deprotect the alde-
hyde. Once the reaction was complete, the product was pu-
rified by flash chromatography (5%–10% methanol in
dichloromethane) to afford 64 mg of the aldehyde (43%
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1
yield). H NMR (400 MHz, CDCl3, ppm) d: 10.05 (1H, s),
7.92 (4H, s), 3.76 (2H, m), 3.69 (4H, m), 3.62 (2H, m).
MS (positive ESI, M + 1) m/z 238.3; (negative ESI, M – 1)
m/z 236.1.
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Acknowledgements
This work has been generously supported by funding from
Genome Canada and the Genomics and Health Initiative of
the National Research Council of Canada. The authors thank
Dr. J. Hulse, Dr. Z. He, and Ms. S. Moisa for XPS assis-
tance.
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