Nitrogen → 5-(But-1-yn-1-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d][1,2,3]triazole

Temperature

0 °C

A 200-mL round-bottom flask equipped with a magnetic stir bar, a rubber septum and N2 inlet was charged with 5-ethynyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d][1,2,3]triazole (2.5 g, 11 mmol) and anhydrous THF (110 mL). This solution was then cooled down to 0° C. in an ice bath. Then, a solution of LiHMDS (27 mL, 1M THF, 27 mmol) was added dropwise over 15 minutes. The resulting mixture was stirred for 1 h at 0° C. To this mixture at 0° C., iodoethane (4.4 mL, 55 mmol) was added dropwise over 5 minutes. The mixture was gradually warmed to room temperature, stirred for 1 h, and then heated at reflux overnight. The reaction was monitored by LCMS. Upon completion, the reaction mixture was cooled down to room temperature, quenched with water (100 mL), and extracted with ethyl acetate (2×100 mL). The combined organics were washed with water (100 mL), washed with brine (50 mL), dried over sodium sulfate, filtered, and concentrated to give the crude product. This crude material was purified on a silica gel column eluted with 5% ethyl acetate in hexanes affording the title compound as a pale yellow oil (1.6 g). 1H NMR (300 MHz, DMSO-d6): δ 7.92 (s, 1H), 7.85 (dd, 1H), 7.33 (dd, 1H), 6.01 (dd, 1H), 3.86-3.80 (m, 1H), 3.75-3.64 (m, 1H), 2.45-2.36 (m, 3H), 2.08-1.91 (m, 2H), 1.74-1.62 (m, 1H), 1.58-1.50 (m, 2H), 1.11 (t, 3H); LCMS: 172 [(M-THP+H)+H]+.

1. customA 200-mL round-bottom flask equipped with a magnetic stir bar
2. temperatureThe mixture was gradually warmed to room temperature
3. stirringstirred for 1 h
4. temperatureheated
5. temperatureat reflux overnight
6. temperatureUpon completion, the reaction mixture was cooled down to room temperature
7. customquenched with water (100 mL)
8. extractionextracted with ethyl acetate (2×100 mL)
9. washThe combined organics were washed with water (100 mL)
10. washwashed with brine (50 mL)
11. dry with materialdried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated

ORD record

ord-a64eaa75ea334ddbabec63a06edd70c2

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09399646B2