2,5-Dimethylpyridine → 6,7-Dihydro-5H-cyclopenta[b]pyridine 1-oxide

HRID 879685Notes

Reaction equation

HRID 879685 reaction equation
C[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=1.NC(N)=O.[OH:13]O.O.[CH3:16][CH2:17]OC(C)=O>>[N+:3]1([O-:13])[C:4]2[CH2:17][CH2:16][CH2:8][C:5]=2[CH:6]=[CH:7][CH:2]=1

Participants

4

Reactant 3

HCID 115262,5-DimethylpyridineHCID 31294Carbamide PeroxideHCID 22728543Water ethylacetate

Product 1

HCID 131533156,7-Dihydro-5H-cyclopenta[b]pyridine 1-oxide

Conditions

Temperature
85 °C

Procedure

N-Oxide Formation. 5 g of 2,5-dimethyl-pyridine and 8.8 g urea-hydrogen peroxide adduct were heated together to 85° C. The mixture melted and was stirred for 18 h at 85° C. It was then cooled to rt and taken up in water-EtOAc and layers separated. The product containing aqueous layer was treated with solid NaCl and concentrated under reduced pressure and back-extracted several times with EtOAc. The back-extracted organic solution was concentrated and the product crystallized. Three crops were collected by filtration for a total of 3.73 g 2,5-dimethyl-pyridine 1-oxide. LCMS (m/z) 124. N-oxide formation also was performed under the following conditions. To a 6,7-dihydro-5H-[1]pyrindine solution in DCM at 0° C. was added peracetic acid (3 mL, 32% in AcOH), and the reaction was slowly allowed to come to rt and stirred for 12 h. The reaction mixture was diluted with DCM (5 mL) and washed with water, aq NaHCO3, brine, then dried over Na2SO4, filtered and concentrated to afford desired 6,7-dihydro-5H-[1]pyrindine 1-oxide (0.6 g). LCMS (m/z): 136.

Workup

  1. temperatureIt was then cooled to rt
  2. customlayers separated
  3. additionThe product containing aqueous layer
  4. additionwas treated with solid NaCl
  5. concentrationconcentrated under reduced pressure
  6. extractionback-extracted several times with EtOAc
  7. concentrationThe back-extracted organic solution was concentrated
  8. customthe product crystallized
  9. filtrationThree crops were collected by filtration for a total of 3.73 g 2,5-dimethyl-pyridine 1-oxide
  10. additionTo a 6,7-dihydro-5H-[1]pyrindine solution in DCM at 0° C. was added peracetic acid (3 mL, 32% in AcOH)
  11. customto come to rt
  12. stirringstirred for 12 h
  13. additionThe reaction mixture was diluted with DCM (5 mL)
  14. washwashed with water, aq NaHCO3, brine
  15. dry with materialdried over Na2SO4
  16. filtrationfiltered
  17. concentrationconcentrated

Sources & evidence

ORD record
ord-1a142ef0e97a40cfab27762b854cb709
Source dataset
uspto-grants-2015_03
Patent number
US08987295B2

Reaction notes

Loading…