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

This compound was prepared according to a procedure similar to that described in Procedure C. In a 100-mL 3-necked round-bottom flask, s-BuLi (1.3M in hexane 10 mL) was added dropwise into a solution of 2-bromo-5-fluoropyridine (1.76 g, 10.00 mmol, 1.00 equiv) in ethyl ether (20 mL) under −76° C. The resulting solution was stirred for 1 h, then 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 NH4Cl (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 mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in 2.2 g (crude) of 2-(5-fluoropyridin-2-yl)-4-(trimethylsilyl)but-3-yn-2-ol as brown oil. In a 50-mL round-bottom flask, potassium carbonate (2.8 g, 20.29 mmol, 2.19 equiv) was added batchwise into a solution of 2-(5-fluoropyridin-2-yl)-4-(trimethylsilyl)but-3-yn-2-ol (2.2 g, 9.27 mmol, 1.00 equiv) in methanol (25 mL). The resulting solution was stirred for 2 h at room temperature. When completed monitored by TLC and LCMS, 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 resulting solution 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 700 mg (46%) of 2-(5-fluoropyridin-2-yl)but-3-yn-2-ol as a light brown solid.

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 NH4Cl (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. dry with materialThe mixture was dried over anhydrous sodium sulfate
7. concentrationconcentrated under vacuum
8. customThis resulted in 2.2 g (crude) of 2-(5-fluoropyridin-2-yl)-4-(trimethylsilyl)but-3-yn-2-ol as brown oil
9. stirringThe resulting solution was stirred for 2 h at room temperature
10. concentrationwas concentrated under vacuum
11. additionThe residue was diluted with 20 mL of water
12. extractionThe resulting solution was extracted with 3×20 mL of ethyl acetate
13. washThe resulting mixture was washed with 1×20 mL of brine
14. filtrationThe solids were filtered out
15. dry with materialThe resulting solution was dried over anhydrous sodium sulfate
16. concentrationconcentrated under vacuum
17. customThis resulted in 700 mg (46%) of 2-(5-fluoropyridin-2-yl)but-3-yn-2-ol as a light brown solid

ORD record

ord-af8552fdbf784cb7b246d13a0958c4a5

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09034866B2