5-ethynyl-2-hydroxybenzaldehyde

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-ethynylsalicylaldehyde (2{26}, 50 mg, 0.34 mmol, 1.0 equiv.) and benzyl azide (91 mg, 86 μL, 0.68 mmol, 2.0 equiv.) were suspended in 1:1 t-BuOH:H2O (1.2 mL). Sodium L-ascorbate (24 mg in 100 μL H2O, 0.34 mmol, 1.0 equiv.) was added, followed by copper (II) sulfate pentahydrate (67 mg in 200 μL H2O, 0.10 mmol, 0.33 equiv.). The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with H2O (10 mL), and the aqueous layer was extracted with DCM (3×10 mL). The combined organic layers were washed with brine (10 mL), dried over Mg504, filtered, and concentrated. The crude product was purified by silica gel column chromatography (25-50% EtOAc/hexanes) to yield 2{27} (47.5 mg, 0.17 mmol, 50.0%) as an off-white solid. 1H-NMR (500 MHz, CDCl3): δ 11.03 (s, 1H), 9.92 (s, 1H), 8.07 (d, 1H, J=2.5 Hz), 7.86 (dd, 1H, J=2.0, 8.0 Hz), 7.65 (s, 1H), 7.41-7.35 (m, 3H), 7.31 (dd, 2H, J=2.0, 7.5 Hz), 7.01 (d, 1H, J=8.5 Hz), 5.57 (s, 2H). 13C-NMR (125 MHz, CDCl3): δ 196.5, 161.3, 134.4, 134.2, 130.6, 129.1, 128.8, 128.1, 124.9, 122.9, 120.6, 118.9, 118.1, 54.3. the aqueous layer was extracted with DCM (3×10 mL) The combined organic layers were washed with brine (10 mL) dried over Mg504 filtered concentrated The crude product was purified by silica gel column chromatography (25-50% EtOAc/hexanes)