Trimethyl orthoformate → 1-((4-methoxyphenyl)methyl)-1H-1,2,3,4-tetrazole

Temperatur

80 °C

The mixture of 4-methoxybenzylamine (27 g), trimethylorthoformate (52.4 ml), sodium azide (19.2 g) and acetic acid (176 ml) was stirred at 80° C. for 14 h. The reaction mixture was concentrated under reduced pressure, the residue was dissolved in water and extracted with ethyl acetate. The extract was washed with a 1N aqueous solution of hydrochloric acid, water, a saturated aqueous solution of sodium hydrocarbonate and a saturated aqueous solution of sodium chloride, successively, dried over anhydrous sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1) to give 1-(4-methoxyphenylmethyl)tetrazole (17.6 g). To a solution of the thus obtained 1-(4-methoxyphenylmethyl)tetrazole (12.0 g) in tetrahydrofuran (240 ml) was added N-bromosuccinimide (16.8 ml) under an atmosphere of argon. The reaction mixture was stirred at room temperature for 3 h. The mixture was quenched by adding a saturated aqueous solution of sodium thiosulfate and concentrated. To the residue was added water and then the mixture was extracted with ethyl acetate. The extract was washed with water and a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=3:1) to give the title compound (15.6 g) having the following physical data.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. dissolutionthe residue was dissolved in water
3. extractionextracted with ethyl acetate
4. washThe extract was washed with a 1N aqueous solution of hydrochloric acid, water
5. dry with materiala saturated aqueous solution of sodium hydrocarbonate and a saturated aqueous solution of sodium chloride, successively, dried over anhydrous sodium sulfate
6. concentrationconcentrated
7. customThe residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:1)

ORD-Eintrag

ord-2049cfd1493a4808be04dccb6c29a5e2

Quelldatensatz

uspto-grants-1998_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05710153