Chloroacetyl chloride → 7,8-Difluoro-6-methoxycarbonyl-4H-benzo[1,4]oxazine-3-one

HRID 495443Notes

Reaction equation

HRID 495443 reaction equation
[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[C:8]([NH2:10])[C:7]([OH:11])=[C:6]([F:12])[C:5]=1[F:13].C(=O)([O-])O.[Na+].Cl[CH2:21][C:22](Cl)=[O:23]>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.C(Cl)(Cl)Cl>[F:13][C:5]1[C:4]([C:3]([O:2][CH3:1])=[O:14])=[CH:9][C:8]2[NH:10][C:22](=[O:23])[CH2:21][O:11][C:7]=2[C:6]=1[F:12]

Participants

6

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 516892Sodium BicarbonateHCID 450896375-Amino-2,3-difluoro-4-hydroxy-benzoic acid methyl ester

Product 1

HCID 223266717,8-Difluoro-6-methoxycarbonyl-4H-benzo[1,4]oxazine-3-oneYield 56.1%

Reagents, catalysts & solvents 2

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 6212ChloroformSolvent

Procedure

A mixture of 5-amino-2,3-difluoro-4-hydroxy-benzoic acid methyl ester (5.5 g, 27.1 mmol) and benzyl-triethylammonium chloride (6.2 g) in chloroform (300 mL) was warmed and sonicated until most of the solid was dissolved. The mixture was cooled in an ice bath and sodium hydrogen carbonate (10 g) was added, followed by chloroacetyl chloride (2.4 mL, 29 mmol). The combined mixture was stirred in cold for 1 hour and then under reflux for approximately 9 hours. It was then evaporated in vacuo and the resulting residue was treated with water and chloroform to give a solid. This solid was collected by filtration, washed with water, diethyl ether and dried in vacuo to give the title compound (3.7 g, 56%).

Workup

  1. temperaturewas warmed
  2. customsonicated until most of the solid
  3. dissolutionwas dissolved
  4. temperatureThe mixture was cooled in an ice bath
  5. temperatureunder reflux for approximately 9 hours
  6. customIt was then evaporated in vacuo
  7. additionthe resulting residue was treated with water and chloroform
  8. customto give a solid
  9. filtrationThis solid was collected by filtration
  10. washwashed with water, diethyl ether
  11. customdried in vacuo

Sources & evidence

ORD record
ord-9c9d064983b3443e875b621f54cc65f7
Source dataset
uspto-grants-2005_09
Patent number
US06939871B2

Reaction notes

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