1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 17947306, compound

Participants

Reaction Steps

Lithium aluminum hydride (95 mg, 2.49 mmol) was added to a solution of 2-benzyloxy-5-ethynyl-benzoic acid benzyl ester (680 mg, 1.99 mmol) in THF (5 mL) at 0° C. After 15 minutes, the reaction was quenched by the sequential addition of water (100 μL), 15% NaOH (100 μL), and water (300 μL). The mixture was diluted with ethyl acetate (10 mL) and dried (MgSO4), filtered, and concentrated. The residue was purified by flash chromatography (10% ethyl acetate/hexanes) to afford 600 mg of a ˜1:1 mixture of 2-benzyloxy-5-ethynyl-benzyl alcohol and 2-benzyloxy-5-ethenyl-benzyl alcohol. This mixture was dissolved in toluene (8 mL) and treated with DBU (0.7 mL, 4.52 mmol) and diphenyl phosphoryl azide (1.1 mL, 5.12 mmol) at room temperature. After 18 hours, water was added and the mixture was extracted with ethyl acetate (3×). The combined organic layers were washed with 1N HCl (1×), brine (1×), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography (3.5% THF/hexanes) and the mixed fractions were rechromatographed with 3% ether/pet ether to afford 206 mg of 2-benzyloxy-5-ethenyl-benzyl azide as the faster eluting fraction. MS 238 (M−N2)+. 1H NMR (400 MHz, CDCl3) δ 7.4 (m, 7H); 6.95 (d, 1H, J=9.1 Hz); 6.62 (dd, 1H, J=17.5, 10.5 Hz); 5.61 (d, 1H, J=17.5 Hz); 5.15 (m, 3H); 4.40 (s, 2H).

Provenance & Evidence