Acetic Acid → HCID 89649817, compound

HRID 2207609Notes

Reaction equation

HRID 2207609 reaction equation
[NH2:1][CH:2]1[CH2:6][CH2:5][N:4]([CH3:7])[C:3]1=[O:8].S([O-])([O-])(=O)=O.[Mg+2].[CH3:15][C:16]1[N:21]=[C:20]([CH:22]=O)[CH:19]=[CH:18][CH:17]=1.[CH:24](S(C1C=CC=CC=1)(=O)=O)=[CH2:25].CC(C)([O-])C.[K+].C(O)(=O)C>C1COCC1.C([O-])(=O)C.[Ag+]>[CH3:7][N:4]1[C:3](=[O:8])[C:2]2([CH2:25][CH2:24][C:22]([C:20]3[CH:19]=[CH:18][CH:17]=[C:16]([CH3:15])[N:21]=3)=[N:1]2)[CH2:6][CH2:5]1

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 24083Sulfuric acid magnesium salt (1:1)HCID 707376-Methyl-2-pyridinecarboxaldehydeHCID 79664Phenyl vinyl sulfoneHCID 23665647Potassium tert-butoxideHCID 457911333-Amino-1-methylpyrrolidin-2-one

Product 1

HCID 89649817HCID 89649817, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 11246Silver acetateCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-amino-1-methyl-pyrrolidin-2-one (9.52 g, 83.38 mmol) in THF (40 mL) was added magnesium sulfate (10035.85 mg, 83.38 mmol) and 6-methylpyridine-2-carbaldehyde (10.1 g, 83.38 mmol) and the reaction was stirred for 16 hours. The reaction was filtered and concentrated in vacuo. To this was added THF (40 mL), and phenyl vinyl sulfone (14024.51 mg, 83.38 mmol) was subsequently added. Silver acetate (139.16 mg, 0.8300 mmol) was then added and the reaction was placed in an ice bath. The reaction was then stirred for 6 hours while allowing to warm to room temperature. The reaction mixture was concentrated in vacuo, methanol added and evaporated again, dissolved in dry THF (120 mL), cooled in an ice bath, and potassium tert-butoxide (16.3 g, 145.26 mmol) was added portionwise. The reaction was quenched by addition of acetic acid (9.55 mL, 166.75 mmol). The reaction was subsequently concentrated in vacuo, dissolved in DCM (500 mL) and then filtered, and the filtrate was concentrated in vacuo. The solid material was recrystallised from acetone. Filtrate and mother liquors were purified by silica column chromatography eluting with a gradient of MeOH in EtOAc. Fractions containing product were combined and crystallised from hot acetone. A total of 13.1 g, (85% yield) of racemic 8-methyl-3-(6-methyl-2-pyridyl)-4,8-diazaspiro[4.4]non-3-en-9-one was obtained;

Workup

  1. filtrationThe reaction was filtered
  2. concentrationconcentrated in vacuo
  3. additionwas subsequently added
  4. customthe reaction was placed in an ice bath
  5. stirringThe reaction was then stirred for 6 hours
  6. concentrationThe reaction mixture was concentrated in vacuo, methanol
  7. additionadded
  8. customevaporated again
  9. dissolutiondissolved in dry THF (120 mL)
  10. temperaturecooled in an ice bath
  11. concentrationThe reaction was subsequently concentrated in vacuo
  12. dissolutiondissolved in DCM (500 mL)
  13. filtrationfiltered
  14. concentrationthe filtrate was concentrated in vacuo
  15. customThe solid material was recrystallised from acetone
  16. customFiltrate and mother liquors were purified by silica column chromatography
  17. washeluting with a gradient of MeOH in EtOAc
  18. additionFractions containing product
  19. customcrystallised from hot acetone

Sources & evidence

ORD record
ord-9ac1049e466346c188be55b3d5e3645f
Source dataset
uspto-grants-2016_06
Patent number
US09376436B2

Reaction notes

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