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

HRID 1193409Notes

Reaction equation

HRID 1193409 reaction equation
[CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:12]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][N:13]=1>C1COCC1>[CH2:1]([O:8][C:12]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][N:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 244Benzyl AlcoholHCID 24758Sodium hydrideHCID 335152,4-Dichloropyridine

Product 1

HCID 543280722-(Benzyloxy)-4-chloropyridineYield 27%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Benzyl alcohol (1.7 ml, 16.326 mmol, 1.2 eq) was added at 0° C. to a suspension of NaH (1.088 g, 27.21 mmol, 2.0 eq) in THF (50 ml) and the mixture was stirred for 30 minutes. A solution of 2,4-dichloropyridine (2.0 g, 13.605 mmol, 1.0 eq) in THF (10 ml) was added dropwise and stirring was carried out for 2 hours at RT. After monitoring by TLC, the reaction mixture was hydrolyzed with ice-water (60 ml) and extracted with ethyl acetate (2×120 ml). The combined org. phases were washed with sat. NaCl solution (100 ml), dried over sodium sulfate, concentrated under reduced pressure and purified by column chromatography (silica gel, 1% ethyl acetate in hexane). Yield: 27% (800 mg, 3.653 mmol)

Workup

  1. stirringstirring
  2. waitwas carried out for 2 hours at RT
  3. extractionextracted with ethyl acetate (2×120 ml)
  4. washphases were washed with sat. NaCl solution (100 ml)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. custompurified by column chromatography (silica gel, 1% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-d933b47ca15142f2a6abdf146ed68d3b
Source dataset
uspto-grants-2014_03
Patent number
US08680159B2

Reaction notes

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