2-Bromo-4-methylpyridine → 2-(4-Methylpyridin-2-yl)but-3-yn-2-ol

Temperature

-78 °C

This compound was prepared according to a procedure similar to that described in Procedure C. Into a 250-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 2-bromo-4-methylpyridine (8.5 g, 49.41 mmol, 1.00 equiv) in tetrahydrofuran (110 mL). This was followed by the addition of n-BuLi (22 mL, 1.20 equiv) dropwise with stirring at −78° C. The resulting solution was stirred for 30 min at −78° C. To this was added 4-(trimethylsilyl)but-3-yn-2-one (7.6 g, 54.19 mmol, 1.10 equiv) dropwise with stirring at −78° C. The resulting solution was warmed slowly to 0° C. and stirred for 10 min at this temperature. The reaction was then quenched by the addition of 10 mL of sat. aq. ammonium chloride. The resulting solution was extracted with 2×40 mL of ethyl acetate and the organic layers combined and dried over sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with petroleum ether:ethyl acetate (5:1). This resulted in 6.5 g (56%) of 2-(4-methylpyridin-2-yl)-4-(trimethylsilyl)but-3-yn-2-ol as colourless oil. Into a 250-mL round-bottom flask, was placed a suspension of 2-(4-methylpyridin-2-yl)-4-(trimethylsilyl)but-3-yn-2-ol (6.5 g, 27.85 mmol, 1.00 equiv) and potassium fluoride dihydrate (6.6 g, 2.50 equiv) in methanol (50 mL). The resulting solution was stirred for 4 h at 50° C. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 100 mL of ethyl acetate. The resulting mixture was washed with 2×50 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:5). This resulted in 3.5 g (78%) of 2-(4-methylpyridin-2-yl)but-3-yn-2-ol as a pink solid.

1. customThis compound was prepared
2. customInto a 250-mL 3-necked round-bottom flask purged
3. temperaturemaintained with an inert atmosphere of nitrogen
4. stirringThe resulting solution was stirred for 30 min at −78° C
5. stirringwith stirring at −78° C
6. temperatureThe resulting solution was warmed slowly to 0° C.
7. stirringstirred for 10 min at this temperature
8. customThe reaction was then quenched by the addition of 10 mL of sat. aq. ammonium chloride
9. extractionThe resulting solution was extracted with 2×40 mL of ethyl acetate
10. dry with materialdried over sodium sulfate
11. concentrationconcentrated under vacuum
12. customThis resulted in 6.5 g (56%) of 2-(4-methylpyridin-2-yl)-4-(trimethylsilyl)but-3-yn-2-ol as colourless oil
13. customInto a 250-mL round-bottom flask, was placed
14. stirringThe resulting solution was stirred for 4 h at 50° C
15. concentrationThe resulting mixture was concentrated under vacuum
16. additionThe resulting solution was diluted with 100 mL of ethyl acetate
17. washThe resulting mixture was washed with 2×50 mL of brine
18. dry with materialThe mixture was dried over anhydrous sodium sulfate
19. concentrationconcentrated under vacuum
20. customThis resulted in 3.5 g (78%) of 2-(4-methylpyridin-2-yl)but-3-yn-2-ol as a pink solid

ORD record

ord-d25c5e89c88f4f79b5a93f19ead41fa2

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09034866B2