反应详情

温度

65 °C

Tert-butyl 5-((diphenoxyphosphoryl)oxy)-2H-1,4-oxazine-4(3H)-carboxylate (20 g, 46.1 mmol) and (4-methoxycarbonylphenyl)boronic acid (9.0 g, 49.8 mmol) were dissolved in acetonitrile (300 ml). A solution of potassium phosphate (19.6 g, 92.3 mmol) in water (75 ml) was added, followed by bis(tri-tert-butylphosphine)palladium (0) (2.36 g, 4.61 mmol). Nitrogen was bubbled through the stirred mixture for 40 minutes, then the mixture was heated to 65° C. for 2 hours. The mixture was cooled and diluted with ethyl acetate (1 L) and water (200 ml). The organic phase was separated and washed with sat NaHCO3 (3×200 ml), then brine (200 ml), dried (MgSO4), filtered and partially concentrated to 50 ml. Solid material was removed by filtration (700 mg). The filtrate was concentrated to a brown solid. The crude was purified on silica gel, eluting with 0-10% ethyl acetate/petrol. This gave the title compound as a white solid (7.4 g, 50%); 1H-NMR (CDCl3) 1.13 (9H, s), 3.80 (2H, t), 3.93 (3H, s), 4.20 (2H, t), 6.36 (1H, s), 7.31 (2H, d), 7.98 (2H, d); 13C-NMR (CDCl3) 27.7, 41.5, 52.0, 66.8, 124.5, 129.6, 133.7; MS ES(+) 264.1 (M+-tBu); Anal. Calcd for C12H21NO5: C, 63.94; H, 6.63; N, 4.38. Found: C, 63.83; H, 6.53; N, 2.23.

1. customNitrogen was bubbled through the stirred mixture for 40 minutes
2. temperatureThe mixture was cooled
3. additiondiluted with ethyl acetate (1 L) and water (200 ml)
4. customThe organic phase was separated
5. washwashed with sat NaHCO3 (3×200 ml)
6. dry with materialbrine (200 ml), dried (MgSO4)
7. filtrationfiltered
8. concentrationpartially concentrated to 50 ml
9. customSolid material was removed by filtration (700 mg)
10. concentrationThe filtrate was concentrated to a brown solid
11. customThe crude was purified on silica gel
12. washeluting with 0-10% ethyl acetate/petrol