Dimethylformamide → 956723-13-0

Temperature

-78 °C

To a stirred, pre-cooled solution of 1-phenethyl-1H-pyrazole (1.10 g, 6.39 mmol) in THF (30 mL) at −78° C., was added dropwise n-BuLi (4.8 mL, 7.66 mmol; 1.6 M in hexane) at such a rate that the internal temperature stayed below −70° C. The mixture was stirred at −78° C. for 1.5 h, during which time the anion precipitated out as a yellow solid. Then DMF (1.25 mL, 15.97 mmol) was added neat and dropwise, and the reaction stirred at −78° C. for 90 min when TLC indicated the reaction was not progressing any further. It was quenched with NH4Cl solution (10 mL), allowed to warm to rt and extracted with EtOAc (4×50 mL). The combined organic extracts were washed with water, brine, dried (Na2SO4), filtered and concentrated. Purification by flash chromatography (Isco CombiFlash) 0-10% EtOAc/heptane provided 2-phenethyl-2H-pyrazole-3-carbaldehyde (540 mg, 43%). 1H NMR (400 MHz, CDCl3) δ ppm 3.09-3.15 (m, 2H), 4.74-4.80 (m, 2H), 6.88 (d, J=2.10 Hz, 1H), 7.16-7.20 (m, 2H), 7.20-7.32 (m, 3H), 7.58 (d, J=2.01 Hz, 1H), 9.77 (s, 1H); LCMS-MS (ESI+) 200.88 (M+H).

1. customstayed below −70° C
2. customprecipitated out as a yellow solid
3. stirringdropwise, and the reaction stirred at −78° C. for 90 min when TLC
4. customIt was quenched with NH4Cl solution (10 mL)
5. temperatureto warm to rt
6. extractionextracted with EtOAc (4×50 mL)
7. washThe combined organic extracts were washed with water, brine
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated
11. customPurification by flash chromatography (Isco CombiFlash) 0-10% EtOAc/heptane

ORD record

ord-95995a252a3248fdb93516b1b853e98a

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07884124B2