Pyridine → HCID 22279538, compound

HRID 1063353Notes

Reaction equation

HRID 1063353 reaction equation
C[NH:2][C:3]([CH3:9])=[CH:4][C:5]([O:7][CH3:8])=[O:6].N1C=CC=CC=1.[Cl:16][CH2:17][C:18]1[CH:26]=[CH:25][C:21]([C:22](Cl)=[O:23])=[CH:20][CH:19]=1>O1CCCC1>[Cl:16][CH2:17][C:18]1[CH:26]=[CH:25][C:21]([C:22]2[O:23][N:2]=[C:3]([CH3:9])[C:4]=2[C:5]([O:7][CH3:8])=[O:6])=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 701364-(Chloromethyl)benzoyl chlorideHCID 2734182Methyl 3-(methylamino)but-2-enoate

Product 1

HCID 22279538HCID 22279538, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methyl 3-oxobutanoate (29.4 g) was dissolved in methanol (30.0 ml), and a 40%-methylamine-methanol solution (32.0 ml) was added dropwise at room temperature. The mixture was stirred for 1 hour. After the completion of the reaction, the reaction solution as such was concentrated, and then dried using a vacuum pump. Thus, methyl 3-(methylamino)-2-butenoate (31.8 g, yield 97%) was obtained. Subsequently, methyl 3-(methylamino)-2-butenoate (5.38 g) was dissolved in tetrahydrofuran (100 ml), and pyridine (5.0 ml) was added dropwise at room temperature. Under ice cooling, p-chloromethyl benzoyl chloride (8.0 g) was added dropwise and the mixture was stirred at room temperature for 4 hours. After the completion of the reaction, distilled water was added, and the product was extracted by liquid separation using ether and then washed with saturated aqueous solution of sodium chloride. The product was dried over sodium sulfate to concentrate and the residue was dried using a vacuum pump. Subsequently, the residue was dissolved in acetic acid (30.0 ml). Hydroxylamine hydrochloride (2.8 g) was added at room temperature, and the mixture was heated under reflux for 1 hour and 30 minutes. After the completion of the reaction, saturated aqueous solution of sodium hydrogencarbonate was added to neutralize the reaction system, and the product was extracted by liquid separation using ether. The resultant organic layer was washed with saturated solution of sodium chloride and dried over sodium sulfate to concentrate. The residue was purified through a column using a hexane-acetone elution system. Thus, methyl 5-[4-(chloromethyl)phenyl]-3-methyl-4-isoxazole carboxylate (5.42 g, yield 49.0%) was obtained.

Workup

  1. customAfter the completion of the reaction
  2. distillationdistilled water
  3. additionwas added
  4. extractionthe product was extracted by liquid separation
  5. washwashed with saturated aqueous solution of sodium chloride
  6. dry with materialThe product was dried over sodium sulfate
  7. concentrationto concentrate
  8. customthe residue was dried
  9. dissolutionSubsequently, the residue was dissolved in acetic acid (30.0 ml)
  10. additionHydroxylamine hydrochloride (2.8 g) was added at room temperature
  11. temperaturethe mixture was heated
  12. temperatureunder reflux for 1 hour and 30 minutes
  13. customAfter the completion of the reaction, saturated aqueous solution of sodium hydrogencarbonate
  14. additionwas added
  15. extractionthe product was extracted by liquid separation
  16. washThe resultant organic layer was washed with saturated solution of sodium chloride
  17. dry with materialdried over sodium sulfate
  18. concentrationto concentrate
  19. customThe residue was purified through a column
  20. washa hexane-acetone elution system

Sources & evidence

ORD record
ord-5caaf84edf17432298c3ea58ffd1b991
Source dataset
uspto-grants-2005_11
Patent number
US06964975B2

Reaction notes

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