反应详情

温度

22.5 °C

To a solution of 4-chloro-2-iodophenol (899 g, 1 eq) and 4-chloro-2-fluorobenzyl bromide (700 g, 1.02 eq) in acetone (8.1 L) was added anhydrous potassium carbonate (926 g). The stirred suspension was then heated to reflux for 30 minutes. 0.12% starting material was observed by HPLC. The product mixture was cooled to 20-25° C. HPLC showed complete consumption of starting material. Inorganic material was then removed by filtration. The residue was washed with acetone (3.6 L) and the combined filtrate and washes were concentrated to 5 vol by atmospheric distillation. Isooctane (4.5 L) was added and reconcentrated to 5 vol by atmospheric distillation. This was repeated once more. The solution was then cooled from 85° C. to 75° C. No precipitation occurred. The batch was then cooled further to 55° C. over 30 minutes, leading to the formation of an immobile suspension. The batch was re-heated to 65° C. which thinned the suspension. The batch was then cooled to 55° C. over 30 minutes. This caused a more controlled precipitation with a mobile suspension.

1. temperatureThe stirred suspension was then heated
2. temperatureto reflux for 30 minutes
3. customconsumption of starting material
4. customInorganic material was then removed by filtration
5. washThe residue was washed with acetone (3.6 L)
6. concentrationthe combined filtrate and washes were concentrated to 5 vol by atmospheric distillation
7. additionIsooctane (4.5 L) was added
8. distillationreconcentrated to 5 vol by atmospheric distillation
9. temperatureThe solution was then cooled from 85° C. to 75° C
10. customNo precipitation
11. temperatureThe batch was then cooled further to 55° C. over 30 minutes
12. temperatureThe batch was re-heated to 65° C. which
13. temperatureThe batch was then cooled to 55° C. over 30 minutes
14. customa more controlled precipitation with a mobile suspension