Cyclopentanol → 2-Cyclopentyloxy-5-nitro-pyridine

HRID 657245Notes

Reaction equation

HRID 657245 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1.[CH:11]1([OH:16])[CH2:15][CH2:14][CH2:13][CH2:12]1.[H-].[Na+]>C1COCC1>[CH:11]1([O:16][C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=2)[CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

5

Reactant 3

HCID 7298CyclopentanolHCID 24758Sodium hydrideHCID 783082-Chloro-5-nitropyridine

Product 1

HCID 150095792-Cyclopentyloxy-5-nitro-pyridineYield 4.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-chloro-5-nitropyridine (7.01 g, 44.4 mmol) in THF (30 mL) and cyclopentanol (3.9 g, 45.3 mmol) was added sodium hydride (1.3 g, 54.2 mmol) portionwise with stirring over ˜30 sec with ice-bath cooling at 0° C. After stirring at 0° C. for 5 min, the ice bath was removed and the reaction was stirred at rt for 3 h. It was then concentrated in vacuo and the residue was dissolved in DCM and washed extensively with 1 M NaHCO3 and then dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash column chromatography (silica gel, 9:1 Hexane:Ethyl Acetate) to obtain pure 2-cyclopentyloxy-5-nitro-pyridine (0.4 g, 4%). 1H-NMR (300 MHz, CDCl3): δ 9.07 (s, 1H), 8.32 (m, 1H), 6.74 (d, 1H), 5.53 (m, 1H), 2.00 (m, 2H), 1.81 (m, 4H), 1.66 (m, 2H).

Workup

  1. stirringAfter stirring at 0° C. for 5 min
  2. customthe ice bath was removed
  3. stirringthe reaction was stirred at rt for 3 h
  4. concentrationIt was then concentrated in vacuo
  5. dissolutionthe residue was dissolved in DCM
  6. washwashed extensively with 1 M NaHCO3
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by flash column chromatography (silica gel, 9:1 Hexane:Ethyl Acetate)

Sources & evidence

ORD record
ord-c712af4f094942628b91a136b8c6e839
Source dataset
uspto-grants-2011_12
Patent number
US08071768B2

Reaction notes

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