反应详情

温度

70 °C

A 250-mL round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with zinc (2.54 g, 38.9 mmol), DMF (32 mL), and dibromomethane (736 mg, 4.24 mmol). After stirring at 70° C. for 10 min, the reaction mixture was cooled to room temperature, and chlorotrimethylsilane (423 mg, 3.89 mmol) was added. The resulting mixture was stirred at room temperature for 30 min, and a solution of 1-(tert-butoxycarbonyl)-3-iodoazetidine (9.31 g, 38.9 mmol) in DMF (32 mL) was added. After stirring at 40° C. for 1 h, a solution of 2-chloro-4-iodo-pyridine (10.0 g, 35.3 mmol) in DMF (16 mL) was added, followed by a solution of (dibenzylideneacetone)dipalladium(0) (1.62 g, 1.77 mmol) and tri(2-furyl)-phosphine (820 mg, 3.53 mmol) in DMF (16 mL). After stirring at 70° C. for 16, the reaction mixture was partitioned between saturated aqueous ammonium chloride (200 mL) and diethyl ether (200 mL). The layers were separated, and the aqueous phase was extracted with diethyl ether (200 mL). The organic extracts were combined, dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by column chromatography to afford a 54% yield (5.42 g) of 117a as a yellow oil: 1H NMR (500 MHz, CDCl3) δ 8.29 (d, 1H, J=2.5 Hz), 7.70 (dd, 1H, J=8.5, 2.5 Hz), 7.35 (d, 1H, J=8.5 Hz), 4.37 (t, 2H, J=8.5 Hz), 3.91 (dd, 2H, J=8.5, 4.5 Hz), 3.73 (m, 1H), 1.46 (s, 9H); MS (ESI+) m/z 269.0 (M+H).

1. customA 250-mL round-bottomed flask equipped with a magnetic stirrer
2. temperaturereflux condenser
3. temperaturethe reaction mixture was cooled to room temperature
4. stirringThe resulting mixture was stirred at room temperature for 30 min
5. stirringAfter stirring at 40° C. for 1 h
6. stirringAfter stirring at 70° C. for 16
7. customthe reaction mixture was partitioned between saturated aqueous ammonium chloride (200 mL) and diethyl ether (200 mL)
8. customThe layers were separated
9. extractionthe aqueous phase was extracted with diethyl ether (200 mL)
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationThe filtrate was concentrated under reduced pressure
13. customThe resulting residue was purified by column chromatography