Hydrochloric Acid → 6-Chloro-2h-1,3-benzoxazine-2,4(3h)-dione

Temperature

2.5 °C

5-chlorosalicylamide (300 g, 1.75 mol) and water (900 ml) were placed in a 3 liter, 4-neck round-bottomed flask under a nitrogen atmosphere and stirred. 5-ethyl-2-methyl-pyridine (284 g, 2.27 mol) and n-butyl acetate (900 ml) were added to the mixture. The mixture was cooled to 0-5° C. (jacket-10° C.) and dropwise addition of ethyl chloroformate (233 g, 2.10 mol) was started. This addition continued over a period of approximately one hour. When the addition was completed, the reaction mixture was slowly heated (in about two hours) to reflux and kept under reflux for an additional period of about 5 hours (jacket 110° C., internal temperature (IT) 90° C.). The resulting slurry was allowed to cool to room temperature, and hydrochloric acid (28 ml, 37% m/m, 0.34 mol) was added and the mixture stirred for about 30 minutes. The resulting slurry was vacuum filtered, the filter cake was washed with n-butyl acetate followed by water (600 ml) and was allowed to dry overnight in vacuo at 60° C. 321 g (93%) of 6-chloro-2H-1,3-benzoxazine-2,4(3H)-dione (6-chloro carsalam) was isolated after drying.

1. additionThis addition
2. additionWhen the addition
3. temperaturethe reaction mixture was slowly heated (in about two hours)
4. temperatureto reflux
5. temperatureunder reflux for an additional period of about 5 hours (jacket 110° C., internal temperature (IT) 90° C.)
6. temperatureto cool to room temperature
7. stirringthe mixture stirred for about 30 minutes
8. filtrationfiltered
9. washthe filter cake was washed with n-butyl acetate
10. customto dry overnight in vacuo at 60° C

ORD record

ord-8e70ce4c6a0e4055bbc271a7f078c33a

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08461385B2