Hydrochloric Acid → ethyl 1-(3,4-difluorophenyl)-1H-1,2,4-triazole-3-carboxylate

Temperature

0 °C

To a solution of 3,4-difluoroaniline (1 mL, 10 mmol) in 5.4 mL of H2O at 0° C. was added 2.8 mL of conc. HCl followed by NaNO2 (1.0 g, 15 mmol, 1.5 eq). The mixture was stirred at 0° C. for 30 min. An additional amount of NaNO2 (0.35 g, 5 mmol, 0.5 eq) was added and the mixture was stirred for 1 h at 0° C. To a separate solution of NaOAc (8.9 g, 108 mmol, 11 eq) in 13 mL EtOH/H2O (12:1) was added ethyl-2-isocyanoacetate (1.1 mL, 10 mmol, 1 eq). The mixture was cooled to 0° C. and the diazonium salt mixture was added dropwise. After stirring for 1 h, the reaction was quenched with H2O and extracted with EtOAc. The organic layer was dried with Na2SO4 and concentrated in vacuo. Purification by silica gel flash chromatography (hex:EtoAc 1:1) afforded ethyl 1-(3,4-difluorophenyl)-1H-1,2,4-triazole-3-carboxylate (0.30 g, 1.3 mmol, 13%).

1. stirringthe mixture was stirred for 1 h at 0° C
2. temperatureThe mixture was cooled to 0° C.
3. stirringAfter stirring for 1 h
4. customthe reaction was quenched with H2O
5. extractionextracted with EtOAc
6. dry with materialThe organic layer was dried with Na2SO4
7. concentrationconcentrated in vacuo
8. customPurification by silica gel flash chromatography (hex:EtoAc 1:1)

ORD record

ord-5667fa7130ec48d1827bea0716f0a4ab

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09169261B2