Hydrochloric Acid → (2,3-Dimethylpyridin-4-YL)methanamine

Temperature

23 °C

To a solution of NaBH4 (65 g, 0.28 mol) in THF (150 ml) was added dropwise BF3-diethyletherate (119.2 g, 0.84 mol) at 0° C. The reaction mixture was stirred for 20 minutes at 23° C. before adding dropwise a solution of 4-cyano-2,3-dimethylpyridine (18.5 g, 0.14 mol, prepared according to J. Heterocycl. Chem. 27 (6), 1990, 1751) in THF (100 ml). The resulting reaction mixture was refluxed for 6 h. Subsequently the reaction mixture was slowly hydrolyzed with water (200 ml) and the pH-value was adjusted to pH 2 with aqueous hydrochloric acid (10% strength). The resulting reaction mixture was refluxed for another 2 hours. Subsequently the reaction mixture was poured onto water and extracted with MTBE. The aqueous layer was adjusted to pH 14 with an aqueous sodium hydroxide solution (50% strength) and extracted once more with DCM. The combined organic layers were dried and the solvent was removed in vacuo. The residue was purified by column chromatography (SiO2, MTBE) to yield 4-(aminomethyl)-2,3-dimethylpyridine as an oily substance (16.5 g). 1H-NMR (CDCl3): δ=1.7 (s, 2H), 2.3 (s, 3H), 2.5 (s, 3H), 3.9 (s, 2H), 7.15 (d, 1H) and 8.3 ppm (d, 2H).

1. customThe resulting reaction mixture
2. temperaturewas refluxed for 6 h
3. customThe resulting reaction mixture
4. temperaturewas refluxed for another 2 hours
5. additionSubsequently the reaction mixture was poured onto water
6. extractionextracted with MTBE
7. extractionextracted once more with DCM
8. customThe combined organic layers were dried
9. customthe solvent was removed in vacuo
10. customThe residue was purified by column chromatography (SiO2, MTBE)

ORD record

ord-52520713ac7f4d848dbe5080da1d46d1

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08299262B2