Oxalyl chloride → 3-(2-Chlorophenyl)-5-(2-benzoxazolyl)-1-phenyl-1,2-dihydropyridin-2-one

HRID 229687Notes

Reaction equation

HRID 229687 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9](=[O:24])[N:10]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:11]=[C:12]([C:14]([O:16][CH3:17])=O)[CH:13]=1.Br[C:26]1[C:27](=O)[N:28](C2C=CC=CC=2)[CH:29]=[C:30](C(OC)=O)[CH:31]=1.ClC1C=CC=CC=1B(O)O.C(Cl)(=O)C(Cl)=O>ClCCl.CN(C)C=O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9](=[O:24])[N:10]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:11]=[C:12]([C:14]2[O:16][C:17]3[CH:29]=[CH:30][CH:31]=[CH:26][C:27]=3[N:28]=2)[CH:13]=1

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 27343222-Chlorophenylboronic acidHCID 223189503-Bromo-5-methoxycarbonyl-1-phenyl-1,2-dihydropyridin-2-oneHCID 223190963-(2-Chlorophenyl)-5-methoxycarbonyl-1-phenyl-1,2-dihydropyridin-2-one

Product 1

HCID 223191453-(2-Chlorophenyl)-5-(2-benzoxazolyl)-1-phenyl-1,2-dihydropyridin-2-one

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

19 mg of carboxylate obtained by hydrolyzing the ester group of 3-(2-chlorophenyl)-5-(methoxycarbonyl)-1-phenyl-1,2-dihydropyridin-2-one (synthesized from 3-bromo-5-(methoxycarbonyl)-1-phenyl-1,2-dihydropyridin-2-one and 2-chlorophenylboronic acid in accordance with the method of Referential Example 3) was dissolved in 20 ml of dichloromethane. Under ice-cooling, a solution of 11 mg of oxalyl chloride in dichloromethane was added dropwise thereinto and a catalytic amount of dimethylformamide was added thereto, followed by stirring at room temperature in nitrogen atmosphere for 1 hour. The reaction solution was evaporated, and the residue was dissolved in dichloromethane. The solution was added dropwise into a solution of 19 mg of 2-aminophenol in dichloromethane under ice-cooling. After heating to room temperature, dichlotomethane was evaporated. To the residue was added 1 ml of polyphosphoric acid, followed by stirring at 180° C. overnight. After cooling to room temperature, the reaction mixture was neutralized with 1N aqueous solution of sodium hydroxide and saturated aqueous solution of sodium hydrogen carbonate under ice-cooling. The mixture was extracted with ethyl acetate, and the resulting organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (hexane/ethylacetate system), to give 3 mg of the title compound as white crystals.

Workup

  1. temperatureUnder ice-cooling
  2. customThe reaction solution was evaporated
  3. dissolutionthe residue was dissolved in dichloromethane
  4. additionThe solution was added dropwise into a solution of 19 mg of 2-aminophenol in dichloromethane under ice-
  5. temperaturecooling
  6. temperatureAfter heating to room temperature
  7. customdichlotomethane was evaporated
  8. additionTo the residue was added 1 ml of polyphosphoric acid
  9. stirringby stirring at 180° C. overnight
  10. temperatureAfter cooling to room temperature
  11. temperaturecooling
  12. extractionThe mixture was extracted with ethyl acetate
  13. washthe resulting organic layer was washed with brine
  14. dry with materialdried over anhydrous magnesium sulfate
  15. customThe solvent was evaporated
  16. customthe residue was purified by silica gel chromatography (hexane/ethylacetate system)

Sources & evidence

ORD record
ord-39b56c6389d947f094e95d72b5420729
Source dataset
uspto-grants-2009_07
Patent number
US07563811B2

Reaction notes

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