反应详情

温度

55 °C

A solution of Example 1C (4.154 kg), potassium carbonate (2.522 kg), and 4-bromophenol (3.183 kg) in acetonitrile (30.3 kg) was stirred at 70° C. for 23.5 hours, cooled to 55° C., treated with 2% (w/w) K2CO3 (41.52 kg) over 20 minutes, cooled to room temperature, and separated into an aqueous fraction and an organic fraction. The organic fraction was concentrated to approximately one third of its original volume, treated with the aqueous fraction to provide a precipitate, concentrated to remove the remainder of the acetonitrile, treated with the 2% (w/w) K2CO3 solution (41.52 kg), stirred at room temperature for 18 hours, and filtered. The filter cake was rinsed with 2% K2CO3 (16.62 L) air-dried, slurried in ethyl acetate (9.44 kg), and heated at 55° C. This solution was treated with hexanes (23.615 kg) and cooled to room temperature to provide a solid. The solid was filtered, rinsed with a solution of ethyl acetate (2.24 kg) and hexanes (7.3 kg), air dried, and vacuum dried (100 mnu/Hg) at 50° C. with a nitrogen bleed to provide 3.307 kg (79.6%, >99.5% ee) of the desired compound. 1H NMR (300 MHz, DMSO-d6) δ7.91 (br s, 1H), 7.47 (dd, J=17 Hz, 2H), 6.93 (dd, J=17 Hz, 2H), 4.44 (m, 1H), 4.15 (m, 2H), 3.95 (m, 2H).

1. temperaturecooled to room temperature
2. customseparated into an aqueous fraction
3. concentrationThe organic fraction was concentrated to approximately one third of its original volume
4. additiontreated with the aqueous fraction
5. customto provide a precipitate
6. concentrationconcentrated
7. customto remove the remainder of the acetonitrile
8. additiontreated with the 2% (w/w) K2CO3 solution (41.52 kg)
9. filtrationfiltered
10. washThe filter cake was rinsed with 2% K2CO3 (16.62 L)
11. customair-dried
12. temperatureheated at 55° C
13. additionThis solution was treated with hexanes (23.615 kg)
14. temperaturecooled to room temperature
15. customto provide a solid
16. filtrationThe solid was filtered
17. washrinsed with a solution of ethyl acetate (2.24 kg) and hexanes (7.3 kg), air
18. customdried
19. customvacuum dried (100 mnu/Hg) at 50° C. with a nitrogen