反应详情

温度

45 °C

To a 400 L glass-lined reactor containing the 4-(1,1-dioxido-4-thiomorpholinyl)-3,5-difluoroaniline/tetrahydrofuran solutions (Step 3, 12.6 kg, 48 moles, 1.0 eq) is added a 47% potassium carbonate solution (14.1 kg, 48 moles, 1.0 eq). The mixture is heated to approximately 45° C., and isobutyl chloroformate (7.2 kg, 53 moles, 1.1 eq) is added while maintaining a reaction temperature between 45° C. and 55° C. The reaction is stirred at 45–55° C. Once complete, the reaction is quenched by slowly adding water (45 L) over 15 minutes. The reaction mixture is cooled to 25° C. and the phases are separated. The tetrahydrofuran solution is swapped to an isopropanol (150 L)/water (50 L) suspension, and the slurry is slowly cooled to 5° C. The yellow slurry is then filtered and the cake washed with cold isopropanol (2×30 L). The yellow solids are dried with 60° C. nitrogen to give the title compound, 1H NMR (CDCl3) δ 7.02 (m, 2H), 6.81 (s, 1H), 3.95 (d, 2H), 3.60 (m, 4H), 3.17 (m, 4H), 1.97 (m, 1H), 0.94 (d, 6H).

1. temperaturewhile maintaining a reaction temperature between 45° C. and 55° C
2. customOnce complete, the reaction is quenched by slowly adding water (45 L) over 15 minutes
3. temperatureThe reaction mixture is cooled to 25° C.
4. customthe phases are separated
5. temperaturethe slurry is slowly cooled to 5° C
6. filtrationThe yellow slurry is then filtered
7. washthe cake washed with cold isopropanol (2×30 L)
8. customThe yellow solids are dried with 60° C. nitrogen