Water → 3-[(Cyclopent-3-en-1-yl)methyl]-2-methoxypyridine

HRID 272595Notes

Reaction equation

HRID 272595 reaction equation
[CH:1]1([C:6]([C:8]2[C:9]([O:14][CH3:15])=[N:10][CH:11]=[CH:12][CH:13]=2)=O)[CH2:5][CH:4]=[CH:3][CH2:2]1.O.NN.[OH-].[K+].O>C(O)CO>[CH:1]1([CH2:6][C:8]2[C:9]([O:14][CH3:15])=[N:10][CH:11]=[CH:12][CH:13]=2)[CH2:2][CH:3]=[CH:4][CH2:5]1

Participants

6

Reactant 4

HCID 962WaterHCID 14797Potassium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 59837860(Cyclopent-3-en-1-yl)(2-methoxypyridin-3-yl)methanone

Product 1

HCID 598378653-[(Cyclopent-3-en-1-yl)methyl]-2-methoxypyridineYield 51%

Reagents, catalysts & solvents 1

HCID 174Ethylene GlycolSolvent

Procedure

Cyclopent-3-enyl-(2-methoxy-pyridin-3-yl)-methanone (10.0 g, 49.3 mmol), hydrazine hydrate (6.33 g, 198 mmol) and pulverized potassium hydroxide (85% KOH) (16.8 g, 300 mmol) were warmed in ethylene glycol (100 mL) until solution occurred at 100° C. then to 180° C. for 18 h. The mixture was cooled to room temperature and treated with water (100 mL) then extracted with 50% EtOAc/hexanes (3×80 mL). The organic layer was washed with saturated aqueous NaCl solution, dried over Na2SO4 and concentrated to an oil. Purification by chromatography on silica gel eluting with 10% EtOAc/hexanes provided the desired product as an oil 4.75 g (51%). (TLC 10% Et2O/hexanes Rf 0.80); 1H NMR (400 MHz, CDCl3) δ 8.01 (dd, J=5.0, 1.7 Hz, 1H), 7.37 (dd, J=7.2, 1.5 Hz, 1H), 6.81 (dd, J=7.2, 5.0 Hz, 1H), 5.66 (s, 2H), 3.95 (s, 3H), 2.61 (m, 3H), 2.40 (m, 2H), 2.03 (m, 2H); GCMS m/z 189 (M)+. 3-Cyclopent-3-enyl-1H-pyrazolo[3,4-b]pyridine was also isolated 4.45 g (49%).

Workup

  1. customoccurred at 100° C.
  2. extractionthen extracted with 50% EtOAc/hexanes (3×80 mL)
  3. washThe organic layer was washed with saturated aqueous NaCl solution
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated to an oil
  6. customPurification by chromatography on silica gel eluting with 10% EtOAc/hexanes

Sources & evidence

ORD record
ord-0448a2383afd4b9ca650a64faa2b3d6f
Source dataset
uspto-grants-2008_11
Patent number
US07456177B2

Reaction notes

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