反应详情

温度

210 °C

A mixture of the 3,5-dibromo-1-p-methoxy-benzyloxybenzene (250 mg, 0.672 mmol) and 3-hydroxypyridine (128 mg, 1.34 mmol) and 96 mg (0.67 mmol) copper oxide in 3 mL of collidine was treated with sodium hydride (27 mg, 0.67 mmol) in a stirred tube. After 10 minutes to allow off-gassing, the tube was sealed and the reaction mixture was heated to 210° C. bath temperature overnight. It was then cooled and treated with ethyl acetate and aqueous ammonium hydroxide, and filtered through Celite®. The phases were separated, and the aqueous phase was extracted with additional ethyl acetate. The combined organics were washed with brine, dried over sodium sulfate and concentrated. The product was chromatographed (33% ethyl acetate/hexane) to give 66 mg of product 3-[3-bromo-5-(4-methoxy-benzyloxy)-phenoxy]-pyridine (25% yield). This material was converted to 3-(1H-indol-4-yl)-5-(pyridin-3-yloxy)-phenol as described in Example 35. 1H NMR (400 MHz, CD3OD): δ 11.22 (s, 1H), 9.77 (s, 1H), 8.43 (d, J=2.5 Hz, 1H), 8.36 (d, J=3.5 Hz, 1H), 7.53 (ddd, J=8.4, 2.7,1.3 Hz, 1H), 7.42 (dd, J=8.4, 4.7Hz, 1H), 7.36 (dd, J=5.4, 2.4Hz, 2H), 7.11 (t, J=7.7 Hz, 1H), 7.00 (d, J=7.0 Hz, 1H), 6.86 (s, 1H), 6.65 (s, 1H), 6.45 (s, 1H), 6.40 (t, J=2.0 Hz, 1H).

1. customthe tube was sealed
2. temperatureIt was then cooled
3. filtrationfiltered through Celite®
4. customThe phases were separated
5. extractionthe aqueous phase was extracted with additional ethyl acetate
6. washThe combined organics were washed with brine
7. dry with materialdried over sodium sulfate
8. concentrationconcentrated
9. customThe product was chromatographed (33% ethyl acetate/hexane)