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

HRID 726588Notes

Reaction equation

HRID 726588 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][NH2:8])=[CH:5][CH:4]=1.[CH3:11]OC(OC)OC.[N-:18]=[N+:19]=[N-:20].[Na+]>C(O)(=O)C>[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][N:8]2[CH:11]=[N:20][N:19]=[N:18]2)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 9005Trimethyl orthoformateHCID 33557Sodium AzideHCID 754524-Methoxybenzylamine

Product 1

HCID 109978051-((4-methoxyphenyl)methyl)-1H-1,2,3,4-tetrazole

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
80 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-2049cfd1493a4808be04dccb6c29a5e2
Source dataset
uspto-grants-1998_01
Patent number
US05710153

Reaction notes

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