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

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 −78 C, 2,4-Dichloro-pyridine was added dropwise while stirring and the mixture was stirred at −78 C for 30 min after which time methyliodide (0.374 mL, 6.0 mmol) was added dropwise at −78 C. This mixture was stirred at −78 C 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.

1. additionwas added dropwise
2. additionwas added dropwise at −78 C
3. additionwas added
4. customto give a reaction mixture pH (wet pH paper) of 5-6
5. washthe organic layer was washed with water (10 mL)
6. dry with materialbrine (10 mL), dried with MgSO4
7. customthe solvent was evaporated in vacuo
8. customto give an oil which
9. customwas purified by flash chromatography

ORD record

ord-99bd83f75b9a4718a8693c743f8782ff

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08546429B2