Dichloromethane → 1-(4-bromo-2-trifluoromethyl-phenyl)-5-methyl-1H-tetrazole

Temperature

0 °C

A suspension of N-(4-bromo-2-trifluoromethyl-phenyl)-acetamide (2.41 g, 8.54 mmol) in acetonitrile (40 mL) was treated with methylene chloride (5 mL) to obtain a clear solution at 25° C. The resulting solution was treated with sodium azide (1.24 g, 19.1 mmol), and the reaction mixture was then cooled to 0° C. The reaction mixture was then treated with trifluoromethanesulfonic anhydride (3.59 g, 12.7 mmol). The resulting reaction mixture was allowed to warm to 25° C. where it was stirred overnight, at which time, thin layer chromatography analysis of the reaction mixture indicated the absence of starting material. The reaction mixture was then concentrated in vacuo. The resulting residue was diluted with ethyl acetate (50 mL) and water (50 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×30 mL). The combined organic extracts were washed with a saturated aqueous sodium chloride solution (1×100 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 2/1 hexanes/ethyl acetate) afforded 1-(4-bromo-2-trifluoromethyl-phenyl)-5-methyl-1H-tetrazole (1.85 g, 70%) as a white solid: EI-HRMS m/e calcd for C9H6BrF3N4 (M+) 305.9728, found 305.9733.

1. customto obtain a clear solution at 25° C
2. customThe resulting reaction mixture
3. temperatureto warm to 25° C. where it
4. concentrationThe reaction mixture was then concentrated in vacuo
5. additionThe resulting residue was diluted with ethyl acetate (50 mL) and water (50 mL)
6. customThe two layers were separated
7. extractionthe aqueous layer was extracted with ethyl acetate (1×30 mL)
8. washThe combined organic extracts were washed with a saturated aqueous sodium chloride solution (1×100 mL)
9. dry with materialdried over anhydrous magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo

ORD record

ord-d401071f4a48474999247420ac7d16a5

Source dataset

uspto-grants-2002_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06369232B1