Thionyl Chloride → 4-Chloro-2-(chloromethyl)pyridine

HRID 1693876Notes

Reaction equation

HRID 1693876 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH2:8]O)[CH:3]=1.S(Cl)([Cl:12])=O.C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH2:8][Cl:12])[CH:3]=1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 2763167(4-Chloropyridin-2-yl)methanol

Product 1

HCID 130529014-Chloro-2-(chloromethyl)pyridineYield 59.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a mixture of (4-chloro-pyridine-2-yl)-methanol (146.8 mg, 1.0 mmol) described in Manufacturing Example 51-1-1 and toluene (3 mL) was added thionyl chloride (112 μL, 1.53 mmol) on an ice bath, which was stirred for 1 hour 15 minutes at room temperature. Saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure and the residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=4:1) to obtain the title compound (97 mg, 59%).

Workup

  1. extractionwas then extracted with ethyl acetate
  2. customThe organic layer was separated
  3. washwashed with water and saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under a reduced pressure
  7. customthe residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=4:1)

Sources & evidence

ORD record
ord-f82b52dd839a4d3a9071764064fef260
Source dataset
uspto-grants-2012_04
Patent number
US08158657B2

Reaction notes

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