反应详情

Palladium (II) EnCat (575 mg, 0.22 mmol) was added to a mixture of potassium carbonate (892 mg, 3.1 mmol), (2R)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]butanamide (1.01 g, 2.1 mmol), (i.e. compound VIIa, which was prepared as in Preparation 8) and 2-(4-bromophenoxy)tetrahydro-2H-pyran (819 mg, 3.18 mmol) in dioxane:water (20 mL, 1:1) in a 50 mL flask and the reaction was heated at 90° C. overnight. The reaction was filtered and the resin was washed with ethyl acetate (50 mL) and water (50 mL). The organic layer was separated and aqueous layer extracted with ethyl acetate (2×100 mL). The combined organics were washed with saturated aqueous sodium bicarbonate (100 mL), dried (MgSO4), filtered and concentrated in vacuo to furnish the crude product. The material was dissolved in a minimum amount of DCM and loaded onto an Analogix SF25-40 g column and eluted with 100% heptane (500 mL) followed by increasing EtOAc in heptane 20%-30%-50% over 500 mL volumes. The title compound was obtained as a white solid (830 mg, 74.4%) LC-MS m/z 530.8 (M−1).

1. filtrationThe reaction was filtered
2. washthe resin was washed with ethyl acetate (50 mL) and water (50 mL)
3. customThe organic layer was separated
4. extractionaqueous layer extracted with ethyl acetate (2×100 mL)
5. washThe combined organics were washed with saturated aqueous sodium bicarbonate (100 mL)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto furnish the crude product
10. washeluted with 100% heptane (500 mL)
11. temperatureby increasing EtOAc in heptane 20%-30%-50% over 500 mL volumes