p-Toluenesulfonic acid → HCID 21834433, compound

HRID 1740988Notes

Reaction equation

HRID 1740988 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][CH2:17][CH2:18][C:19]([O:21][CH3:22])=[O:20])[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][CH2:17][CH2:18][C:19]([O:21][CH3:22])=[O:20])[CH:3]=[C:2]([CH3:1])[CH:7]=1

Participants

8

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 14797Potassium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 23506719HCID 23506719, compound

Product 1

HCID 21834433HCID 21834433, compoundYield 61%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

Methyl 5-(4-methyl-6-(2,5-dimethylpyrrol-1-yl)-2-pyridinyl)pentanoate (330 mg, 1.10 mmol) was dissolved in 6.0 mL of 95% ethanol, and 1.0 mL of water was added followed by 199 mg (3.08 mmol) of 87% potassium hydroxide. After 2 h, an additional 1 mL of water was added along with 351 mg (5.06 mmol) of hydroxylamine hydrochloride. The solution was heated to reflux for 20 h, then cooled and concentrated. The residue was dissolved in 15 mL of 2 N aqueous hydrochloric acid and washed with 2×10 mL of ethyl ether. The aqueous layer was evaporated and triturated with 3×5 mL of methanol. The methanol extracts were evaporated to give 619 mg of partially crystalline material. A portion (495 mg) of this material was dissolved in 6.0 mL of methanol along with 510 mg (2.68 mmol) of p-toluenesulfonic acid and heated to reflux for 20 h. The reaction was cooled and concentrated and the residue was partitioned between 25 mL of saturated aqueous sodium bicarbonate and 50 mL of ethyl acetate. The aqueous layer was extracted with 2×25 mL of ethyl acetate. The combined organic layers were washed with 50 mL of saturated aqueous sodium chloride, dried (sodium sulfate), decanted, and evaporated. The residue was purified by flash column chromatography on 20 g of silica gel, eluting with 500 mL of 50% ethyl acetate in dichloromethane to give 119 mg (61% yield) of methyl 5-(6-amino-4-methyl-2-pyridinyl)pentanoate as an amber oil.

Workup

  1. temperatureThe solution was heated
  2. temperatureto reflux for 20 h
  3. temperaturecooled
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in 15 mL of 2 N aqueous hydrochloric acid
  6. washwashed with 2×10 mL of ethyl ether
  7. customThe aqueous layer was evaporated
  8. customtriturated with 3×5 mL of methanol
  9. customThe methanol extracts were evaporated
  10. customto give 619 mg of partially crystalline material
  11. temperatureheated
  12. temperatureto reflux for 20 h
  13. temperatureThe reaction was cooled
  14. concentrationconcentrated
  15. customthe residue was partitioned between 25 mL of saturated aqueous sodium bicarbonate and 50 mL of ethyl acetate
  16. extractionThe aqueous layer was extracted with 2×25 mL of ethyl acetate
  17. washThe combined organic layers were washed with 50 mL of saturated aqueous sodium chloride
  18. dry with materialdried (sodium sulfate)
  19. customdecanted
  20. customevaporated
  21. customThe residue was purified by flash column chromatography on 20 g of silica gel
  22. washeluting with 500 mL of 50% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-471a902a44894693bc97c75dcccabc3c
Source dataset
uspto-grants-1999_10
Patent number
US05972975

Reaction notes

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