3. Effect of Residence Time on Crisaborole Formation .
| Process
Parameter |
Area % in HPLC |
||||
|---|---|---|---|---|---|
| Residence Time (s) | 10 | 13 | 14 | 15 | Crisaborole (6) |
| 2.0 | 0.10 | 7.93 | 2.20 | 3.30 | 85.00 |
| 1.5 | 0.01 | 6.25 | 0.80 | 2.80 | 89.50 |
| 1.0 | 0.01 | 6.70 | 0.85 | 2.70 | 88.50 |
| 0.5 | 0.01 | 6.80 | 0.88 | 2.60 | 88.20 |
| 0.25 | 0.03 | 6.88 | 0.92 | 2.57 | 88.05 |
| 0.10 | 0.05 | 6.98 | 1.0 | 2.50 | 87.92 |
a
All reactions were conducted using 5.0 g (1.0 equiv) of compound 10, triisopropyl borate at 4.0 equiv, and n-butyllithium at 2.0 equiv under conditions of −60 °C. The residence time was varied as indicated in the accompanying table for the coupling reaction. For cyclization, 3 M HCl was employed at a stoichiometric ratio of 7.0 equiv. The area percentage was assessed at 210 nm using high-performance liquid chromatography (HPLC).