反应详情

温度

2.5 °C

13.4 kg 3-Bromo-6-chloro-indan-1-one (A; for references on this material, see: Bøgesø EP 35363 A1 19810909 and Kehler, Juhl, Püschl, WO 2008025361; each herein incorporated by reference in its entirety) was dissolved in tetrahydrofuran (170.8 L), and the solution was cooled to 0-5° C. (Scheme 9). Triethylamine (9.1 L) was added over 0.5 h. The mixture was stirred at 0-5° C. for 5 hours before an additional portion of triethylamine (2.48 L) was added over 0.5 hour, and stirring was continued for 2 hours. The mixture was filtered, and the filtrate was concentrated to 30 L before n-heptane (102 L) was added. The volume was reduced to 60 L. More n-heptane (203 L) was added, and the mixture was stirred for 1 hour. Silica gel (17.2 kg) was added. The mixture was filtered, and the residual solid was washed with n-heptane (100 L). The combined filtrates were concentrated to 30 L and stirred at 0-5° C. for 1 hour. The mixture was centrifuged, and the residual solid was dried to afford 6-chloro-inden-1-one (compound B; 2.42 kg) sufficiently pure for the next step.

1. additionwas added over 0.5 hour
2. filtrationThe mixture was filtered
3. concentrationthe filtrate was concentrated to 30 L before n-heptane (102 L)
4. additionwas added
5. additionMore n-heptane (203 L) was added
6. stirringthe mixture was stirred for 1 hour
7. additionSilica gel (17.2 kg) was added
8. filtrationThe mixture was filtered
9. washthe residual solid was washed with n-heptane (100 L)
10. concentrationThe combined filtrates were concentrated to 30 L
11. stirringstirred at 0-5° C. for 1 hour
12. customthe residual solid was dried