Reaktion #1779364

Reaktionsgleichung

6-chloro-8-methyl-2H-3,1-benzoxazine-2,4(1H)-dione

6-chloro-8-methyl-2H-3,1-benzoxazine-2,4(1H)-dione

6-chloro-8-methyl-2H-3,1-benzoxazine-2,4(1H)-dione

ethyl acetate

acetic acid

methylamine

→

title compound

Ausbeute 95.6%

2-Amino-5-chloro-N,3-dimethylbenzamide

Ausbeute 95.6%

Lösungsmittel

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeA 300-mL flask equipped with a thermometer and nitrogen bubbler
2. 2
   Temperaturwas cooled
3. 3
   Temperaturto maintain the temperature below 35° C
4. 4
   Temperaturwas maintained at 40-45° C.
5. 5
   workup.DISTILLATIONethyl acetate was distilled out at an internal temperature of about 46-60° C. and pressure of about 30 to 50 kPa
6. 6
   Sonstigeremoved by distillation, water
7. 7
   workup.ADDITIONwas added
8. 8
   Temperaturto maintain the original liquid volume in the reactor
9. 9
   workup.DISTILLATIONto distill
10. 10
    Temperaturthe aqueous slurry was cooled to 10° C
11. 11
    FiltrationThe solid was collected by filtration
12. 12
    Sonstigedried at 60° C.

Vorschrift

A 300-mL flask equipped with a thermometer and nitrogen bubbler was charged with ethyl acetate (100 mL) and 12.6 g (0.21 mol) of acetic acid. Anhydrous methylamine (6.3 g, 0.20 mol) was added below the surface of the liquid mixture, which was cooled to maintain the temperature below 35° C. Then 6-chloro-8-methyl-2H-3,1-benzoxazine-2,4(1H)-dione (21 g, 0.10 mol) (i.e. the product of Example 1) was added in portions while maintaining the reaction mixture at 35-40° C. After completion of the addition of the 6-chloro-8-methyl-2H-3,1-benzoxazine-2,4(1H)-dione the temperature was maintained at 40-45° C., and the progress of the reaction was monitored by HPLC analysis. After about 20 minutes, when no more than 0.5% 6-chloro-8-methyl-2H-3,1-benzoxazine-2,4(1H)-dione remained, water (50 mL) was added. A distillation head was attached, moderate vacuum was applied, and ethyl acetate was distilled out at an internal temperature of about 46-60° C. and pressure of about 30 to 50 kPa. To replace the ethyl acetate removed by distillation, water was added to maintain the original liquid volume in the reactor. When a significant amount of water began to distill, the aqueous slurry was cooled to 10° C. The solid was collected by filtration and dried at 60° C. and 13.3 kPa to afford the title compound as a white crystalline solid (19 g, ca. 95% yield, >98% purity by peak area in HPLC analysis).

Quelle