Potassium Carbonate → 2-(5-Chloropyridin-2-yl)but-3-yn-2-ol

This compound was prepared according to a procedure similar to that described in Procedure C. to a 100-mL 3-necked round-bottom flask, s-BuLi (1.3M in hexane, 10 mL) was added into a solution of 2-bromo-5-chloropyridine (1.92 g, 9.98 mmol, 1.00 equiv) in ethyl ether (20 mL) under −76° C., Stirred for 1 h at this temp., 4-(trimethylsilyl)but-3-yn-2-one (1.54 g, 10.98 mmol, 1.10 equiv) was added. The resulting solution was stirred for 2 h at −76° C. The reaction was then quenched by the addition of 10 mL of ammonium chloride (sat., aq.). The resulting solution was extracted with 3×20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1×20 mL of brine. The solid was dried in an oven under reduced pressure. This resulted in 2.5 g (crude) of 1-(5-chloropyridin-2-yl)-3-(trimethylsilyl)prop-2-yn-1-one as brown oil. In a 50-mL round-bottom flask, potassium carbonate (2.8 g, 20.29 mmol, 2.06 equiv) was added batchwise into a solution of 2-(5-chloropyridin-2-yl)-4-(trimethylsilyl)but-3-yn-2-ol (2.5 g, 9.85 mmol, 1.00 equiv) in methanol (25 mL). The resulting solution was stirred for 2 h at room temperature. TLC indicated the reaction completed, the solvent was concentrated under vacuum. The residue was diluted with 20 mL of water. The resulting solution was extracted with 3×20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1×20 mL of brine. The solids were filtered out. 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 (1:10). This resulted in 800 mg (45%) of 2-(5-chloropyridin-2-yl)but-3-yn-2-ol as brown oil.

1. customThis compound was prepared
2. stirringThe resulting solution was stirred for 2 h at −76° C
3. customThe reaction was then quenched by the addition of 10 mL of ammonium chloride (sat., aq.)
4. extractionThe resulting solution was extracted with 3×20 mL of ethyl acetate
5. washThe resulting mixture was washed with 1×20 mL of brine
6. customThe solid was dried in an oven under reduced pressure
7. customThis resulted in 2.5 g (crude) of 1-(5-chloropyridin-2-yl)-3-(trimethylsilyl)prop-2-yn-1-one as brown oil
8. stirringThe resulting solution was stirred for 2 h at room temperature
9. concentrationthe solvent was concentrated under vacuum
10. additionThe residue was diluted with 20 mL of water
11. extractionThe resulting solution was extracted with 3×20 mL of ethyl acetate
12. washThe resulting mixture was washed with 1×20 mL of brine
13. filtrationThe solids were filtered out
14. dry with materialThe mixture was dried over anhydrous sodium sulfate
15. concentrationconcentrated under vacuum
16. customThis resulted in 800 mg (45%) of 2-(5-chloropyridin-2-yl)but-3-yn-2-ol as brown oil

ORD record

ord-4d7b12cce8a34991a7a6bce313149451

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09034866B2