Acetone Cyanohydrin → HCID 178492038, compound

HRID 240328Notes

Reaction equation

HRID 240328 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:14](=[O:15])[C:13]([C:16](O)=[O:17])=[N:12][C:11]3[CH:19]=[CH:20][CH:21]=[N:22][C:10]2=3)=[CH:5][CH:4]=1.C(Cl)(=O)C(Cl)=O.[C:29]1(=[O:36])[CH2:34][CH2:33][CH2:32][C:31](=[O:35])[CH2:30]1.C(N(CC)CC)C.CC(C)(O)C#N.[OH-].[Na+]>ClCCl.O.CN(C)C=O>[OH:36][C:29]1[CH2:34][CH2:33][CH2:32][C:31](=[O:35])[C:30]=1[C:16]([C:13]1[C:14](=[O:15])[N:9]([C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)[C:10]2[N:22]=[CH:21][CH:20]=[CH:19][C:11]=2[N:12]=1)=[O:17]

Participants

10

Reactant 6

HCID 6406Acetone CyanohydrinHCID 8471Triethylamine2×HCID 104341,3-CyclohexanedioneHCID 14798Sodium HydroxideHCID 65578Oxalyl chlorideHCID 67532047HCID 67532047, compound

Product 1

HCID 178492038HCID 178492038, compoundYield 78%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Procedure

4.4 g (15 mmol) of 4-(4-methoxyphenyl)-3-oxo-3,4-dihydropyrido[2,3-b]pyrazine-2-carboxylic acid was dissolved in dichloromethane (100 mL), and to this solution, N,N-dimethylformamide (0.5 mL) and 3.8 g (30 mmol) of oxalyl chloride were added sequentially. The mixture was heated to reflux for one hour while stirring. After confirming the completion of the reaction, the reaction solution was cooled to room temperature, and the solvent was distilled off under reduced pressure. The residue thus obtained was dissolved in dichloromethane (30 mL), and this solution was added dropwise at 0° C. over 5 minutes to a solution prepared by dissolving 1.8 g (16 mmol) of 1,3-cyclohexanedione and 1.8 g (18 mmol) of triethylamine in dichloromethane (30 mL). The reaction solution was returned to room temperature and stirred for 3 hours, and then acetone cyanohydrin (1 mL) and 1.8 g (18 mmol) of triethylamine were further added thereto. The mixture was stirred for 12 hours at room temperature. After confirming the completion of the reaction, water (20 mL) was added to the reaction solution, the reaction solution was adjusted to pH 12 using a 10% aqueous solution of sodium hydroxide, and the reaction solution was separated. The aqueous layer was adjusted to pH 1 by adding 6 N hydrochloric acid, and then the aqueous layer was extracted with dichloromethane. The obtained organic layer was dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue thus obtained was washed with methanol, to obtain 4.5 g (yield: 78%) of 2-(2-hydroxy-6-oxo-1-cyclohexenecarbonyl)-4-(4-methoxyphenyl)-pyrido[2,3-b]pyrazin-3(4H)-one.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for one hour
  3. customthe completion of the reaction
  4. distillationthe solvent was distilled off under reduced pressure
  5. customThe residue thus obtained
  6. additionthis solution was added dropwise at 0° C. over 5 minutes to a solution
  7. customprepared
  8. customwas returned to room temperature
  9. stirringstirred for 3 hours
  10. stirringThe mixture was stirred for 12 hours at room temperature
  11. additionwas added to the reaction solution
  12. customthe reaction solution was separated
  13. additionby adding 6 N hydrochloric acid
  14. extractionthe aqueous layer was extracted with dichloromethane
  15. dry with materialThe obtained organic layer was dried over anhydrous magnesium sulfate
  16. distillationthe solvent was distilled off under reduced pressure
  17. customThe residue thus obtained
  18. washwas washed with methanol

Sources & evidence

ORD record
ord-dac28127963d4b559e35f5def28f0171
Source dataset
uspto-grants-2014_02
Patent number
US08648075B2

Reaction notes

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