4-Toluenesulfonyl chloride → 2-(Chloromethyl)-3,5-dimethylpyridine

HRID 1842402Notes

Reaction equation

HRID 1842402 reaction equation
S([Cl:11])(C1C=CC(C)=CC=1)(=O)=O.[CH3:12][C:13]1[C:18]([CH3:19])=[CH:17][C:16]([CH3:20])=[CH:15][N+:14]=1[O-].C(N(CC)CC)C>C(Cl)Cl>[Cl:11][CH2:12][C:13]1[C:18]([CH3:19])=[CH:17][C:16]([CH3:20])=[CH:15][N:14]=1

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 104869072,3,5-Trimethyl-1-oxidopyridin-1-ium

Product 1

HCID 155943992-(Chloromethyl)-3,5-dimethylpyridineYield 66.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Tosyl chloride (12.5 g, 65.6 mmol) was added to a solution of 2,3,5-trimethylpyridine 1-oxide (6.0 g, 43.7 mmol), and triethylamine (6.6 g, 65.6 mmol) in DCM (60 ml) at RT under an atmosphere of nitrogen. The reaction mixture was heated to reflux and reflux was maintained 4 h (reaction was monitored by TLC). The reaction was quenched with water and extracted with DCM. The combined organics were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography using 10% ethyl acetate in n-hexanes and silica gel (230-400 Mesh) to afford 2-(chloromethyl)-3,5-dimethylpyridine (4.5 g, 66.1%,) as a brown thick syrup. 1H NMR: 200 MHz, CDCl3: δ 8.15 (s, 1H), 7.45 (s, 1H), 4.75 (s, 2H), 2.35 (s, 3H), 2.25 (s, 3H). MS: [M+H]+: m/z=156.3.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux
  3. temperaturereflux
  4. temperaturewas maintained 4 h
  5. custom(reaction was monitored by TLC)
  6. customThe reaction was quenched with water
  7. extractionextracted with DCM
  8. dry with materialThe combined organics were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-48f7c07a8cad40299fc295241cbd48f0
Source dataset
uspto-grants-2015_02
Patent number
US08946222B2

Reaction notes

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