反应详情

In a 500-mL round bottom flask, cool a solution of 2-[2-(2-benzo[b]thiophen-7-yl-phenoxy)-ethoxy]-tetrahydropyran (500 mg, 1.41 mmol) and triisopropylborate (530 mg, 2.82 mmol) in THF (30 mL) to −70° C. under N2. To the solution, add lithium diisopropylamide (2 M in THF, 1.41 mL, 2.82 mmol) gradually over a period of 30 min. Stir the mixture continually for an additional 1 h in the cooling bath. Gradually transfer the mixture into a refluxing solution of 2,4-dichloro-5-fluoropyrimidine (353 mg, 2.12 mmol), Pd(dppf)Cl2 (57.6 g, 0.07 mmol) and sodium carbonate (2 M in water, 1.8 mL, 3.6 mmol) in THF (20 mL) over a period of 30 min. Reflux for an additional 1 h. Cool the mixture to RT and dilute with chloroform/IPA (3/1) and water. Wash the organic layer with aqueous saturated sodium chloride. Dry over sodium sulfate. Concentrate in vacuo. Purify the residue by FCC (20% ethyl acetate in hexane) to give the title compound (550 mg, 80%). MS (ES) m/z 507 [M+Na]+.

1. temperatureReflux for an additional 1 h
2. washWash the organic layer with aqueous saturated sodium chloride
3. dry with materialDry over sodium sulfate
4. concentrationConcentrate in vacuo
5. customPurify the residue by FCC (20% ethyl acetate in hexane)