Water → 3-(3-Chloro-propoxy)-pyridine

HRID 2305573Notes

Reaction equation

HRID 2305573 reaction equation
[OH:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[H-].[Na+].[Cl:10][CH2:11][CH2:12][CH2:13]I.O>CN(C)C=O>[Cl:10][CH2:11][CH2:12][CH2:13][O:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 79713-HydroxypyridineHCID 24758Sodium hydrideHCID 813631-Chloro-3-iodopropane

Product 1

HCID 184333433-(3-Chloro-propoxy)-pyridineYield 54.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Under a nitrogen atmosphere, a solution of 3-hydroxypyridine (5.00 g, 52.58 mmol) in N,N-dimethylformamide (DMF) (55 mL) was slowly added to a cold (0-5° C.), stirring slurry of sodium hydride (2.52 g of an 80% dispersion in mineral oil, 84.0 mmol) in DMF (10 mL). The mixture was allowed to warm to ambient temperature and further stirred for 1 h. To this slurry was added 1-choro-3-iodopropane (12.90 g, 63.10 mmol), and the resulting dark-brown mixture was stirred at ambient temperature for 48 h. Cold water was added and the mixture was extracted with chloroform (4×100 mL). The combined chloroform extracts were washed with water (2×50 mL), dried (Na2SO4), filtered, and concentrated by rotary evaporation. Water (150 mL) was added, and the mixture was basified with 20% NaOH solution (5.0 mL). The alkaline solution was extracted with methyl t-butyl ether (MTBE) (5×100 mL). The combined MTBE extracts were washed with water (4×100 mL), dried (Na2SO4), filtered, and concentrated by rotary evaporation to give 4.90 g (54.3%) of an oil. 1H NMR (CDCl3, 300 MHz): δ8.34 (s, 1H), 8.24 (s, 1H), 7.22 (t, 2H, J=2.13 Hz), 4.18 (t, 2H, J=5.85 Hz), 3.77 (t, 2H, J=6.19 Hz), 2.27 (p, 2H, J=6.03 Hz). 13C NMR (CDCl3, 75 MHz): δ154.99, 142.38, 138.07, 123.93, 121.09, 64.60, 41.22, 32.11. EI-MS: m/z (relative intensity) 171 (M+, 27.25%), 136 (4.66%), 95 (100.00%), 78 (17.98%), 41 (37.74%), 39 (34.23%).

Workup

  1. stirringthe resulting dark-brown mixture was stirred at ambient temperature for 48 h
  2. extractionthe mixture was extracted with chloroform (4×100 mL)
  3. washThe combined chloroform extracts were washed with water (2×50 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation
  7. additionWater (150 mL) was added
  8. extractionThe alkaline solution was extracted with methyl t-butyl ether (MTBE) (5×100 mL)
  9. washThe combined MTBE extracts were washed with water (4×100 mL)
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated by rotary evaporation

Sources & evidence

ORD record
ord-3aedaed16f0046fda1f53a8ac5af0dfc
Source dataset
uspto-grants-2002_08
Patent number
US06441007B1

Reaction notes

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