Acetic Acid → 2-Amino-5-Chloro-N,3-Dimethylbenzamide

HRID 1692183Notes

Reaction equation

HRID 1692183 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH3:14])[C:5]2[NH:10]C(=O)[O:8][C:7](=O)[C:6]=2[CH:13]=1.C(OCC)(=O)C.C(O)(=O)C.[CH3:25][NH2:26]>O>[NH2:10][C:5]1[C:4]([CH3:14])=[CH:3][C:2]([Cl:1])=[CH:13][C:6]=1[C:7]([NH:26][CH3:25])=[O:8]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6329MethylamineHCID 8857Ethyl AcetateHCID 115502595-Chloro-3-methyl isatoic anhydride

Product 1

HCID 250682512-Amino-5-Chloro-N,3-DimethylbenzamideYield 93%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

A 250-mL flask equipped with a thermometer and nitrogen bubbler was charged with 6-chloro-8-methyl-2H-3,1-benzoxazine-2,4(1H)-dione (9.0 g, 43 mmol) (i.e. the product of Example 1), ethyl acetate (50 mL), and acetic acid (3.8 g, 63 mmol). The mixture was heated to 50° C., and anhydrous methylamine (1.6 g, 50 mmol) was added below the surface of the mixture while maintaining the temperature at 48-52° C. The mixture was held for 1 h at 50° C., then water (65 mL) was added, and the ethyl acetate was removed by distillation. When the pot temperature reached 83° C., the solution was seeded, and the product slurry was cooled over 3 h to 10° C. The solid was collected by filtration and dried to afford the title compound as a white crystalline solid (7.94 g, >98.5 wt. % purity by HPLC assay, 93% yield) melting at 143-145° C.

Workup

  1. customA 250-mL flask equipped with a thermometer and nitrogen bubbler
  2. temperaturewhile maintaining the temperature at 48-52° C
  3. customthe ethyl acetate was removed by distillation
  4. customreached 83° C.
  5. temperaturethe product slurry was cooled over 3 h to 10° C
  6. filtrationThe solid was collected by filtration
  7. customdried

Sources & evidence

ORD record
ord-da85840b415244a685e022c08277d5de
Source dataset
uspto-grants-2012_04
Patent number
US08153844B2

Reaction notes

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