反应详情

温度

-70 °C

To a cooled (-70° C.) solution of n-butylithium (129.3 mL of 1.18 M hexanes solution, 0.153 mol) in isopropyl ether was added a solution of 3-bromo-2,5-dichloropyridine (36.45 g, 0.161 mol) in isopropyl ether (225 mL) over a period of 30 minutes. The resulting white suspension was then treated with a solution of 3(R)-t-butyldimethylsiloxybutyraldehyde (34.14 g, 0.169 mol) in isopropyl ether (106 mL) and allowed to stir for an additional 30 minutes at -70° C. followed by warming to room temperature. After the addition of 480 mL of water, the biphasic mixture was separated and the organic layer was extracted with isopropyl ether (2×200 mL). The combined organic layers were washed once with water, heated with decolorizing carbon [G-60 DARCO (trademark)] filtered through diatomateous earth [Celite (trademark)] and condensed on a rotary evaporator. The resulting hazy yellow liquid was heated at 80° C. under high vacuum overnight to yield the desired product (mixture of diastereomers) as an amber oil (40.52 g, 72%): Rf 0.36 (25% Et2O in hexanes); 1H NMR (60 MHz, CDCl3) δ 0.1 (s, 6H), 0.82 (s, 9H), 1.18 (m, 3H), 1.72 (m, 2H), 4.16 (m, 1H), 4.42 (m, 1H), 5.10 (m, 1H), 7.92 (d, 1H, J=2.6 Hz), 8.13 (d, 1H, J=2.6 Hz).

1. temperatureby warming to room temperature
2. customthe biphasic mixture was separated
3. extractionthe organic layer was extracted with isopropyl ether (2×200 mL)
4. washThe combined organic layers were washed once with water
5. temperatureheated with decolorizing carbon [G-60 DARCO (trademark)]
6. filtrationfiltered through diatomateous earth [Celite (trademark)] and condensed on a rotary evaporator
7. temperatureThe resulting hazy yellow liquid was heated at 80° C. under high vacuum overnight