Methyl iodide → Methyl 2-chloro-3-methylpyridine-4-carboxylate

To a stirred solution of 2-chloro-3-methylpyridine-4-carboxylic acid (780 mg, 4.5 mmol) in anhydrous DMF (5.0 ml), was added potassium carbonate (1.25 g, 9.1 mmol), followed by methyl iodide (0.42 ml, 6.8 mmol) dropwise. A further 4 ml of DMF was added and the reaction mixture was stirred at room temperature under nitrogen for 18.5 hours. The solvent was removed in-vacuo and the residue was then partitioned between CH2Cl2 (20 ml) and water (20 ml). The layers were separated and the aqueous layer was extracted with CH2Cl2 (3×15 ml). The combined organic layers were washed with water (2×30 ml), brine (40 ml), dried (MgSO4), filtered and concentrated in-vacuo. The residue was purified by column chromatography (10 g SNAP cartridge, Isolera, 0-6% ethyl acetate:heptanes) to give the title compound (591 mg, 59%) as a colourless oil. LC-MS 84%, m/z=185.9, 187.9; 1H NMR (500 MHz, Chloroform-d) δ ppm 8.33 (d, J=5.04 Hz, 1H) 7.54 (d, J=5.04 Hz, 1H) 3.95 (s, 3H) 2.60 (s, 3H).

1. customThe solvent was removed in-vacuo
2. customthe residue was then partitioned between CH2Cl2 (20 ml) and water (20 ml)
3. customThe layers were separated
4. extractionthe aqueous layer was extracted with CH2Cl2 (3×15 ml)
5. washThe combined organic layers were washed with water (2×30 ml), brine (40 ml)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated in-vacuo
9. customThe residue was purified by column chromatography (10 g SNAP cartridge, Isolera, 0-6% ethyl acetate:heptanes)

ORD record

ord-ae51b32c3f9f428b8e9cf79c87f080ec

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09376422B2