Acetic Acid → 2,4-Dichloro-3-methylpyridine

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Reaction Steps

1.6 M n-Butyl lithium in hexanes (3.75 mL, 6.0 mmol) and anhydrous THF (5 mL) were added to a flame-dried flask under nitrogen atmosphere. This solution was cooled to −78C, 2,4-Dichloro-pyridine was added dropwise while stirring and the mixture was stirred at −78C for 30 min after which time methyliodide (0.374 mL, 6.0 mmol) was added dropwise at −78C. This mixture was stirred at −78C for 1 h under nitrogen atmosphere after which time glacial AcOH (0.114 mL, 2.0 mmol) was added to give a reaction mixture pH (wet pH paper) of 5-6. The reaction mixture was dissolved in Et2O (100 mL), the organic layer was washed with water (10 mL), then brine (10 mL), dried with MgSO4, and the solvent was evaporated in vacuo to give an oil which was purified by flash chromatography using hexanes:CH2Cl2 (50:50 v/v) to hexanes:CH2Cl2:EtOAc (50:47:3 v/v/v) to give 2,4-dichloro-3-methyl-pyridine as a white solid (589 mg, 72%). It was noted that 2,4-dichloro-3-methyl-pyridine readily sublimates in vacuo. 1H NMR (CD3OD, 400 MHz) δ 8.15 (d, 1H), 7.46 (d, 1H), 2.50 (s, 3H). LRMS calculated for C6H5Cl2N: 160.98, found: (MH)+ 161.9.

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