Dichloromethane → 1-(2-chloro-4-iodo-phenyl)-5-methyl-1H-tetrazole

Temperature

0 °C

A suspension of N-(2-chloro-4-iodo-phenyl)-acetamide (2.39 g, 8.09 mmol) in acetonitrile (40 mL) at 25° C. was treated with methylene chloride (5 mL) to obtain a clear solution. The resulting solution was then treated with sodium azide (1.05 g, 16.18 mmol), and the reaction mixture was cooled to 0° C. The reaction mixture was then treated with trifluoromethanesulfonic anhydride (3.42 g, 12.13 mmol), and the resulting reaction mixture was allowed to warn to 25° C. where it was stirred overnight. The reaction mixture was then concentrated in vacuo. The residue was diluted with ethyl acetate (50 mL) and water (50 mL), and the two layers were separated. The aqueous layer was further extracted with ethyl acetate (1×30 mL). The combined organic layers 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, 4/1 hexanes/ethyl acetate) afforded 1-(2-chloro-4-iodo-phenyl)-5-methyl-1H-tetrazole (1.53 g, 59%) as a white solid: mp 128-130.5° C.; EI-HRMS m/e calcd for C8H6ClIN4 (M+) 319.9327, found 319.9325.

1. customto obtain a clear solution
2. customthe resulting reaction mixture
3. customto warn to 25° C.
4. concentrationThe reaction mixture was then concentrated in vacuo
5. additionThe residue was diluted with ethyl acetate (50 mL) and water (50 mL)
6. customthe two layers were separated
7. extractionThe aqueous layer was further extracted with ethyl acetate (1×30 mL)
8. washThe combined organic layers 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-b03b686a043a4feab88ca151897d2eb0

Source dataset

uspto-grants-2002_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06388088B1