Benzyl Alcohol → 4-(Benzyloxy)-2-chloropyridine

HRID 240545Notes

Reaction equation

HRID 240545 reaction equation
[H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Cl:11][C:12]1[CH:17]=[C:16]([N+]([O-])=O)[CH:15]=[CH:14][N:13]=1>C1COCC1.O>[CH2:3]([O:10][C:16]1[CH:15]=[CH:14][N:13]=[C:12]([Cl:11])[CH:17]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 3

HCID 244Benzyl AlcoholHCID 24758Sodium hydrideHCID 7351522-Chloro-4-nitropyridine

Product 1

HCID 534041974-(Benzyloxy)-2-chloropyridine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.) slurry of washed (hexanes) sodium hydride (14.07 g, 352 mmol) in THF (650 mL) was added dropwise a solution of benzyl alcohol (35.2 mL, 337 mmol) in THF (200 mL). After stirring for 15 minutes, a solution of 2-chloro-4-nitropyridine (50 g, 306 mmol) in THF (200 mL) was added dropwise. After heating to reflux for 16 hours, the black slurry was diluted with water (200 mL) and concentrated to remove the THF. The resulting mixture was diluted with more water and filtered. The filtrate was extracted with ether and ethyl acetate. The combine organics were dried and concentrated. The residue was chromatographed (10% ethyl acetate in hexanes) to provide the product as orange solid.

Workup

  1. temperatureAfter heating
  2. temperatureto reflux for 16 hours
  3. concentrationconcentrated
  4. customto remove the THF
  5. additionThe resulting mixture was diluted with more water
  6. filtrationfiltered
  7. extractionThe filtrate was extracted with ether and ethyl acetate
  8. customThe combine organics were dried
  9. concentrationconcentrated
  10. customThe residue was chromatographed (10% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-40c1966cbabd48af87883053e420bcf8
Source dataset
uspto-grants-2014_02
Patent number
US08648087B2

Reaction notes

Loading…