反应详情

Triphenyl phosphine (124 mg, 0.47 mmol, 1.5 Eq.) was added to a stirred solution of 1-(2-Chloro-phenyl)-ethanol (74 mg, 0.47 mmol, 1.5 Eq.) in anhydrous THF (5 mL) at 0° C. under nitrogen. The reaction was stirred at this temperature for 30 minutes, then diethyl azodicarboxylate (75 μL, 0.47 mmol, 1.5 Eq.) was added dropwise and the reaction stirred at 0° C. for a further 1 hour. 3-Hydroxy-5-(3-phenylamino-[1,2,4]triazol-1-yl)-thiophene-2-carboxylic acid methyl ester (100 mg, 0.32 mmol, 1.0 Eq.) in anhydrous DMF (2 mL) was added and the reaction stirred for a further 1 hour at 0° C. then allowed to warm to ambient temperature overnight. The crude reaction mixture was partitioned between EtOAc (50 mL) and water (50 mL). The organic phase was washed with water (2×20 mL), dried (MgSO4) and concentrated in vacuo. The crude product was purified by column chromatography (ISCO Companion™, 12 g column, 0-100% EtOAc/petroleum Ether) to give the sub-title compound as an off-white solid (88 mg, 0.19 mmol, 73%); 1H NMR (400 MHz, CDCl3) δ 1.74 (3H, d), 3.93 (3H, s), 5.84 (1H, q), 6.70 (1 h, br s), 6.74 (1H, s), 7.02 (1H, t), 7.21-7.40 (5H, m), 7.51 (1H, d), 7.63 (1H, d), 8.12 (1H, s).

1. stirringthe reaction stirred at 0° C. for a further 1 hour
2. stirringthe reaction stirred for a further 1 hour at 0° C.
3. customThe crude reaction mixture
4. customwas partitioned between EtOAc (50 mL) and water (50 mL)
5. washThe organic phase was washed with water (2×20 mL)
6. dry with materialdried (MgSO4)
7. concentrationconcentrated in vacuo
8. customThe crude product was purified by column chromatography (ISCO Companion™, 12 g column, 0-100% EtOAc/petroleum Ether)