反应详情

The title compound was prepared in a similar manner as that described for Example 10, step 4. Into a 25-mL round-bottom flask equipped with a magnetic stirbar was added 2-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-5-ethynylpyrimidine (130 mg, 0.35 mmol), sodium azide (23 mg, 0.35 mmol) tert-butanol (1.5 mL), water (0.7 mL), copper(I) iodide (4 mg, 0.02 mmol) and sodium ascorbate (9 mg, 0.04 mmol). The resulting suspension was treated with dropwise addition of ethyl 2-bromopropionate (45 μL, 0.35 mmol) and stirred at room temperature for 16 h overnight. The mixture was poured into a 125 mL separatory funnel containing water (75 mL) and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and the solvent was evaporated under reduced pressure. Purification by column chromatography through silica gel, eluting with 5% EtOAc in hexanes to 55% EtOAc in hexanes as a gradient gave the desired product as a beige solid.

1. customThe title compound was prepared in a similar manner as
2. customInto a 25-mL round-bottom flask equipped with a magnetic stirbar
3. additionThe mixture was poured into a 125 mL separatory funnel
4. extractionthe mixture was extracted with ethyl acetate (3×50 mL)
5. washThe combined organic layers were washed with brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. customthe solvent was evaporated under reduced pressure
9. customPurification by column chromatography through silica gel
10. washeluting with 5% EtOAc in hexanes to 55% EtOAc in hexanes as a gradient