Thionyl Chloride → 5-(Chloromethyl)-2-(trifluoromethyl)pyridine

HRID 512135

Reaction equation

HRID 512135 reaction equation
S(Cl)([Cl:3])=O.[F:5][C:6]([F:16])([F:15])[C:7]1[N:12]=[CH:11][C:10]([CH2:13]O)=[CH:9][CH:8]=1>C(Cl)Cl>[Cl:3][CH2:13][C:10]1[CH:9]=[CH:8][C:7]([C:6]([F:16])([F:15])[F:5])=[N:12][CH:11]=1

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 36138956-(Trifluoromethyl)pyridine-3-methanol

Product 1

HCID 27738105-(Chloromethyl)-2-(trifluoromethyl)pyridine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Thionyl chloride (40.3 mL, 554 mmol) was slowly added to a solution of (6-trifluoromethylpyridin-3-yl)-methanol (19.6 g, 111 mmol) in DCM (195 mL) at room temperature under nitrogen. The reaction mixture was stirred at reflux for 16 hours then concentrated under reduced pressure. The residue was dissolved in AcOEt (200 mL), washed with saturated aqueous sodium bicarbonate, brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to give crude 5-chloromethyl-2-trifluoromethylpyridine as a brown oil which was used in the following step without further purification (19.5 g, 90%). 1H NMR (400 MHz, CDCl3) δ ppm 8.74 (s, 1 H), 7.94 (d, J=8.4 Hz, 1 H), 7.72 (d, J=8.4 Hz 1H), 4.66 (s, 2 H). 19F NMR (400 MHz, CDCl3) δ 168 cm−1. MS m/z 196.15; 198.09

Workup

  1. temperatureat reflux for 16 hours
  2. concentrationthen concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in AcOEt (200 mL)
  4. washwashed with saturated aqueous sodium bicarbonate, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-71b55fac469c45f183426faa2cebeaec
Source dataset
uspto-grants-2015_08
Patent number
US09102591B2

Linked notes

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