p-Toluenesulfonic acid → 5-Chlorobenzoxazole

Temperature

60 °C

To a 250 mL 3-neck round bottom flask equipped with a distillation head, glass stopper, septum, thermocouple and magnetic stir bar was charged 2-amino-4-chlorophenol (20.00 g, 0.139 mol). The solid was dissolved in THF (60 mL) and p-TsOH (0.265 g, 1.39 mmol) was added. The brown solution was warmed to 60° C. over 10 min and aged for 90 min. HPLC assay of the reaction mixture showed 1 LCAP unreacted starting material. The temperature was increased from 60° C. to 74° C., and at 63° C. solvent distillation began. A total of 58 mL was collected during the first distillation. The mixture was diluted with THF (60 mL) and a total of 67 mL of solvent was removed between 71 and 84° C. The mixture was again diluted with THF (60 mL) and 61 mL of solvent was removed between 74 and 114° C. The dark brown solution was cooled to room temperature. The final mass of the solution was 27.96 g. Analysis of the crude stream by 1H NMR showed 0.1 wt % MeOH present in the sample. 1H NMR (500 MHz, CDCl3): δ=8.10 (s, 1H), 7.76 (d, J=1.5 Hz, 1H), 7.50 (d, J=8.7 Hz, 1H), 7.36 ppm (dd, J=8.7, 1.7 Hz, 1H).

1. customTo a 250 mL 3-neck round bottom flask equipped with a distillation head, glass stopper, septum, thermocouple and magnetic stir bar
2. temperatureThe temperature was increased from 60° C. to 74° C.
3. distillationat 63° C. solvent distillation
4. distillationA total of 58 mL was collected during the first distillation
5. additionThe mixture was diluted with THF (60 mL)
6. customa total of 67 mL of solvent was removed between 71 and 84° C
7. additionThe mixture was again diluted with THF (60 mL) and 61 mL of solvent
8. customwas removed between 74 and 114° C
9. temperatureThe dark brown solution was cooled to room temperature

ORD record

ord-3db72312b4db4d1b8a889bf79aad3f34

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09441254B2