2-Amino-5-chlorobenzoic acid → methyl (E)-3-(6-chloro-4-oxo-4H-benzo[d][1,3]oxazin-2-yl)acrylate

HRID 1641439Notes

Reaction equation

HRID 1641439 reaction equation
CS(Cl)(=O)=O.[C:6]([O:13][CH3:14])(=[O:12])/[CH:7]=[CH:8]\[C:9]([O-:11])=O.[Cl:15][C:16]1[CH:24]=[C:20]([C:21](O)=[O:22])[C:19]([NH2:25])=[CH:18][CH:17]=1>O.N1C=CC=CC=1.C(#N)C>[Cl:15][C:16]1[CH:17]=[CH:18][C:19]2[N:25]=[C:9](/[CH:8]=[CH:7]/[C:6]([O:13][CH3:14])=[O:12])[O:11][C:21](=[O:22])[C:20]=2[CH:24]=1

Participants

7

Reactant 3

HCID 124762-Amino-5-chlorobenzoic acidHCID 31297Methanesulfonyl chlorideHCID 21768182Mono-methyl maleate

Product 1

HCID 13927266methyl (E)-3-(6-chloro-4-oxo-4H-benzo[d][1,3]oxazin-2-yl)acrylateYield 68.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolvent2×HCID 6342AcetonitrileSolvent3×

Procedure

A mixed solution comprising 1.49 g of methanesulfonyl chloride and 10 ml of acetonitrile was cooled with ice, and 10 ml of an acetonitrile solution comprising 1.3 g of monomethyl maleate and 1.34 g of pyridine was dropwise added thereto under cooling with ice over a period of 5 minutes, followed by stirring for 5 minutes at the same temperature. 10 ml of an acetonitrile solution comprising 1.72 g of 5-chloroanthranilic acid and 2.77 g of pyridine was added under cooling with ice over a period of 2 minutes, followed by rinsing with 5 ml of acetonitrile and stirring for 20 minutes at the same temperature. 1.49 g of methanesulfonyl chloride was added over a period of 2 minutes under cooling with ice, followed by rinsing with 2 ml of acetonitrile and stirring for 30 minutes, and then the temperature was returned to room temperature, followed by reaction for 4 hours. The reaction liquid was poured to 20 ml of water, followed by stirring for 30 minutes. The resulting crystals were collected by filtration, washed with water and a mixed liquid of acetonitrile:water (2:1), and dried to obtain 1.82 g of the brown desired product (melting point: 162 to 164° C.).

Workup

  1. additionwas dropwise added
  2. temperatureunder cooling with ice over a period of 5 minutes
  3. additionwas added
  4. temperatureunder cooling with ice over a period of 2 minutes
  5. washby rinsing with 5 ml of acetonitrile
  6. stirringstirring for 20 minutes at the same temperature
  7. addition1.49 g of methanesulfonyl chloride was added over a period of 2 minutes
  8. temperatureunder cooling with ice
  9. washby rinsing with 2 ml of acetonitrile
  10. stirringstirring for 30 minutes
  11. customwas returned to room temperature
  12. customfollowed by reaction for 4 hours
  13. customThe reaction liquid
  14. stirringby stirring for 30 minutes
  15. filtrationThe resulting crystals were collected by filtration
  16. washwashed with water
  17. dry with materiala mixed liquid of acetonitrile:water (2:1), and dried

Sources & evidence

ORD record
ord-4a21735ec87e4ee88bd06cb39c0d2a2f
Source dataset
uspto-grants-2012_02
Patent number
US08115006B2

Reaction notes

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