反应详情

温度

75 °C

An appropriately sized and equipped reaction vessel was charged with 4-iodo-2-methylphenol (75.7 g, 323 mmol) in 380 mL DMF. To that was added Pd(PPh3)4 (3.56 g, 3.08 mmol) at room temperature giving a light yellow solution. Then, 5,5′-(oxybis(ethane-2,1-diyl))bis(bicyclo[2.2.1]hept-2-ene) (39.8 g, 154 mmol), 100 ml dimethylformamide (DMF), and triethylamine (65 mL, 462 mmol) were added and the mixture stirred as formic acid (17.7 g, 14.5 mL 385 mmol) was added drop wise within 5 minutes. The reaction temperature rose from 20° C. to 25° C. after which external heating was applied. At 70° C., an exothermic reaction began and the temperature quickly climbed to 82° C. within 10 minutes accompanied by color changes from light yellow to orange to black. The reaction was monitored by GC and after stirring at 75° C. for 96 h an aliquot GC indicated the reaction was complete. The reaction mixture was allowed to cool to room temperature and was poured into 2000 mL distilled water. The aqueous mixture was extracted with (3×1500 mL) MTBE, the extracts were filtered through a Celite® filtering aid pad to remove palladium particles and then washed with (2×1 L) water, (2×1 L) brine and (2×1 L) 5% aqueous LiCl to remove residual DMF. The resulting MTBE solution was dried over sodium sulfate, filtered, and the solvent rotary evaporated to give 94 g of a brown liquid. The 94 g of crude PP475 was adsorbed onto 120 g silica and chromatographed over an additional 1 kg of silica eluting with heptane-EtOAc mixtures. The concentrated purified fractions yielded 43 g (59% yield) of PP475 as a clear viscous oil with >98.0% purity by NMR. NMR and MS were consistent with the desired structure.

1. customequipped
2. customreaction vessel
3. customgiving a light yellow solution
4. additionwas added drop wise within 5 minutes
5. customrose from 20° C. to 25° C.
6. temperatureexternal heating
7. customAt 70° C., an exothermic reaction
8. temperatureto cool to room temperature
9. additionwas poured into 2000 mL
10. distillationdistilled water
11. extractionThe aqueous mixture was extracted with (3×1500 mL) MTBE
12. filtrationthe extracts were filtered through a Celite®
13. filtrationfiltering aid pad
14. customto remove palladium particles
15. washwashed with (2×1 L) water, (2×1 L) brine and (2×1 L) 5% aqueous LiCl
16. customto remove residual DMF
17. dry with materialThe resulting MTBE solution was dried over sodium sulfate
18. filtrationfiltered
19. customthe solvent rotary evaporated