反应详情

Mixed 4-bromo-2-nitro-6-tetrahydrofuran-2-yl-aniline (6a) (40.40 g, 92%, 129.5 mmol), 1,4-dioxane (260 mL, Sigma-Aldrich 360481), 2-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl]propan-2-ol (7) (41.05 g, 155.4 mmol), and aqueous 2.7 M Na2CO3 (143.9 mL, 388.5 mmol). A stream of nitrogen was bubbled through the stirring mixture for 1 hr, followed by addition of tetrakis(triphenylphosphine)palladium (0) (7.48 g, 6.47 mmol, Strem 462150). The reaction mixture was stirred at reflux for 2 hrs (HPLC showed complete reaction), allowed to cool, diluted with EtOAc, washed with water, saturated aqueous NH4Cl, brine, dried over MgSO4, and filtered through a short plug of Florisil® eluting with EtOAc. The filtrate was concentrated under reduced pressure giving adark brown oil. Dissolved in CH2Cl2 and eluted through a short plug of silica gel with CH2Cl2 and then EtOAc. The desired fraction was concentrated on a rotary evaporator until a precipitate formed giving a thick brown slurry, which was triturated with MTBE. The solid was collected by filtration, washed with MTBE, and dried under high vacuum giving (8) as a yellow solid (35.14 g, 99+% HPLC purity,). LCMS (C18 column eluting with 10-90% CH3CN/water gradient over 5 minutes with formic acid modifier) M+1: 345.00 (2.69 min). 1H NMR (300 MHz, CDCl3) δ 8.88 (s, 2H), 8.36 (d, J=2.2 Hz, 1H), 7.56 (d, J=2.1 Hz, 1H), 7.09 (s, 2H), 4.92 (t, J=7.2 Hz, 1H), 4.62 (s, 1H), 4.20-4.11 (m, 1H), 4.03-3.94 (m, 1H), 2.39-2.26 (m, 1H), 2.23-2.08 (m, 3H), 1.64 (s, 6H) ppm. The filtrate was further concentrated and purified by ISCO silica gel chromatography eluting with 0 to 80% EtOAc/hexane giving a second crop of product (8) as an amber solid (4.46 g, 88% overall yield; 88% HPLC purity.

1. customA stream of nitrogen was bubbled through the stirring mixture for 1 hr
2. temperatureat reflux for 2 hrs
3. custom(HPLC showed complete reaction)
4. temperatureto cool
5. washwashed with water, saturated aqueous NH4Cl, brine
6. dry with materialdried over MgSO4
7. filtrationfiltered through a short plug of Florisil®
8. washeluting with EtOAc
9. concentrationThe filtrate was concentrated under reduced pressure
10. customgiving adark brown oil
11. washeluted through a short plug of silica gel with CH2Cl2
12. concentrationThe desired fraction was concentrated on a rotary evaporator until a precipitate
13. customformed
14. customgiving a thick brown slurry, which
15. customwas triturated with MTBE
16. filtrationThe solid was collected by filtration
17. washwashed with MTBE
18. customdried under high vacuum