Acetone → 4-(6-Chloro-2-methylpyridin-3-yl)-2-methylbut-3-yn-2-ol

Temperatur

-78 °C

6-Chloro-3-ethynyl-2-methylpyridine (Example 432, Step 1) (200 mg, 1.32 mmol) was taken up in 4 ml tert-butyl methyl ether and added to a dry flask under argon. The flask was cooled to −78° C. and allowed to stir for 20 min. Butyllithium (0.99 ml of 1.6 M in hexanes, 1.58 mmol) was added to the reaction mixture dropwise over 30 minutes, and the mixture was allowed to stir as such for 30 min. Acetone (0.13 ml, 1.72 mmol) was taken up in 1 ml tert-butyl methyl ether and added dropwise over 30 min. The reaction mixture was allowed to warm to 0° C. and was stirred as such for 90 minutes. The reaction mixture was then allowed to warm to room temperature and stirred for 1 hour. The reaction mixture was quenched with aqueous sodium bicarbonate and extracted twice with diethyl ether. All organic fractions were combined, dried over anhydrous magnesium sulfate, filtered, and concentrated. The resulting crude product was purified by silica gel chromatography (0-50% ethyl acetate/hexanes) to afford the title compound.

1. additionadded to a dry flask under argon
2. stirringto stir as such for 30 min
3. additionadded dropwise over 30 min
4. temperatureto warm to 0° C.
5. stirringwas stirred as such for 90 minutes
6. temperatureto warm to room temperature
7. stirringstirred for 1 hour
8. customThe reaction mixture was quenched with aqueous sodium bicarbonate
9. extractionextracted twice with diethyl ether
10. dry with materialdried over anhydrous magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated
13. customThe resulting crude product was purified by silica gel chromatography (0-50% ethyl acetate/hexanes)

ORD-Eintrag

ord-728deb7d156342a9994d62fd9e04104d

Quelldatensatz

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08367706B2