反应详情

DBU (1.32 ml; 8.82 mmol; 1.10 eq.) was dissolved in DMF (16.5 ml) and put under nitrogen atmosphere. 3-Oxo-3-(tetrahydro-pyran-4-yl)-propionic acid ethyl ester (Pharmacore, 1.767 g; 8.82 mmol; 1.10 eq.) was added to the mixture and it was stirred for 15 min. Then a solution of 1-azido-2-fluorobenzene, prepared according to Platz, M. S. et al. J. Org. Chem. 1989, 54, 5938-5945, (1.1 g; 8.02 mmol; 1 eq.) in DMF (15 mL) was added dropwise to the solution at room temperature. The reaction mixture was stirred at 70° C. for 2 hours. Water (40 mL) was added to the reaction mixture. The aqueous layer was extracted with EtOAc (3×40 mL). Combined organic layers were washed with HCl 0.1N, brine, dried over MgSO4 and concentrated under vacuum giving the title compound as a yellow oil. It was used in the next step without further purification. LC/MS (Method B): 320.2 (M+H)+.

1. stirringThe reaction mixture was stirred at 70° C. for 2 hours
2. extractionThe aqueous layer was extracted with EtOAc (3×40 mL)
3. washCombined organic layers were washed with HCl 0.1N, brine
4. dry with materialdried over MgSO4
5. concentrationconcentrated under vacuum