p-Toluenesulfonic acid → HCID 53949251, compound

HRID 1740991Notes

Reaction equation

HRID 1740991 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([N:8]2C(C)=CC=C2C)[N:5]=[C:4]([CH2:15][CH2:16][CH:17]([C:23]([O:25][CH2:26]C)=[O:24])[C:18]([O:20][CH2:21]C)=[O:19])[CH:3]=1.[OH-].[K+].Cl.NO.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(O)C.CO.O>[NH2:8][C:6]1[N:5]=[C:4]([CH2:15][CH2:16][CH:17]([C:23]([O:25][CH3:26])=[O:24])[C:18]([O:20][CH3:21])=[O:19])[CH:3]=[C:2]([CH3:1])[CH:7]=1

Participants

8

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 14797Potassium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 54457771HCID 54457771, compound

Product 1

HCID 53949251HCID 53949251, compoundYield 52%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

To a solution of diethyl (2-(4-methyl-6-(2,5-dimethylpyrrol-1-yl)-2-pyridinyl)ethyl)malonate (96 mg, 0.26 mmol) in 1.4 mL of ethanol was added 0.3 mL of water, followed by 105 mg of 87% potassium hydroxide (1.63 mmol). After the mixture had been stirred at room temperature for 7 h., additional water (0.3 mL) was added along with 166 mg (2.39 mmol) of hydroxylamine hydrochloride. The mixture was refluxed 12 h. After removing solvent in vacuo, the residue was dissolved into 10 mL of 2.0 N aqueous hydrochloric acid and washed with 2×10 mL of diethyl ether. The aqueous phase was concentrated and swirled with 3×1 mL of methanol. The methanol extracts were combined, filtered, and evaporated. The residue was dissolved in 5.0 mL of methanol along with 149 mg (0.78 mmol) of p-toluenesulfonic acid and heated to reflux for 16 h. The reaction was cooled and concentrated and the residue was partitioned between 15 mL of saturated aqueous sodium bicarbonate and 30 mL of ethyl acetate. The organic layer was washed with 15 mL of saturated aqueous sodium chloride, dried (sodium sulfate), decanted, and evaporated. The residue was purified by flash column chromatography on 10 g of silica gel, eluting with 200 mL of 40% ethyl acetate in dichloromethane and 200 ML of 50% ethyl acetate in dichloromethane to give 36 mg (52% yield) of dimethyl (2-(6-amino-4-methyl-2-pyridinyl)ethyl)malonate.

Workup

  1. temperatureThe mixture was refluxed 12 h
  2. customAfter removing solvent in vacuo
  3. dissolutionthe residue was dissolved into 10 mL of 2.0 N aqueous hydrochloric acid
  4. washwashed with 2×10 mL of diethyl ether
  5. concentrationThe aqueous phase was concentrated
  6. filtrationfiltered
  7. customevaporated
  8. temperatureheated
  9. temperatureto reflux for 16 h
  10. temperatureThe reaction was cooled
  11. concentrationconcentrated
  12. customthe residue was partitioned between 15 mL of saturated aqueous sodium bicarbonate and 30 mL of ethyl acetate
  13. washThe organic layer was washed with 15 mL of saturated aqueous sodium chloride
  14. dry with materialdried (sodium sulfate)
  15. customdecanted
  16. customevaporated
  17. customThe residue was purified by flash column chromatography on 10 g of silica gel
  18. washeluting with 200 mL of 40% ethyl acetate in dichloromethane and 200 ML of 50% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-6714b629be964cf9a9ff8dde237ba56c
Source dataset
uspto-grants-1999_10
Patent number
US05972975

Reaction notes

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