Reaktion #1750692

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
   Sonstigefor a method of preparation)
5. 5
   workup.ADDITIONwas added in portions
6. 6
   Temperaturwas maintained at 40-45° C.
7. 7
   workup.ADDITIONwas added to the reaction mixture
8. 8
   workup.DISTILLATIONethyl acetate was distilled out at an internal temperature of about 46-60° C. and pressure of about 30 to 50 kPa
9. 9
   Sonstigeremoved by distillation, water
10. 10
    workup.ADDITIONwas added
11. 11
    Temperaturto maintain the original liquid volume in the reactor
12. 12
    workup.DISTILLATIONto distill
13. 13
    Temperaturthe aqueous slurry was cooled to 10° C
14. 14
    FiltrationThe solid was collected by filtration
15. 15
    Sonstigedried at 60° C.

Vorschrift

A 300-mL flask equipped with a thermometer and nitrogen bubbler was charged with ethyl acetate (100 mL) and acetic acid (12.6 g, 0.21 mol). 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., and then 6-chloro-8-methyl-2H-3,1-benzoxazine-2,4(1H)-dione (21 g, 0.10 mol) (see Scheme 4 for a method of preparation) 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. When analysis of the reaction mixture indicated no more than 0.5% of the 6-chloro-8-methyl-2H-3,1-benzoxazine-2,4(1H)-dione remained (about 20 minutes), water (50 mL) was added to the reaction mixture. 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, above 98% purity by peak area in HPLC analysis).

Quelle