Ethyl orthoformate → 3-Bromo-4-(tetrazol-1-yl)anisole

HRID 1003258Notes

Reaction equation

[Br:1][C:2]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:3]=1[NH2:4].[CH2:11](OC(OCC)OCC)C.[N-:21]=[N+:22]=[N-:23].[Na+]>C(O)(=O)C.O>[Br:1][C:2]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:3]=1[N:4]1[CH:11]=[N:23][N:22]=[N:21]1

Participants

Conditions

Temperature: 75 °C

Procedure

2-Bromo-4-methoxyaniline (1.2 g, 6 mmol; Desc. 7a) was dissolved in glacial acetic acid (10 ml) and heated to 75° C. To this solution was added triethylorthoformate (2.5 ml, 15 mmol) and heated at 75° C. for 1 hour. Sodium azide (1.16 g, 18 mmol) was added portionwise and reaction heated at 75° C. for a further 3 hours and stirred at ambient temperature for 24 hours. The reaction was diluted with water (100 ml) and product extracted into ethyl acetate (3×70 ml). The combined organics were washed with brine (100 ml), dried over magnesium sulphate and the solvent removed in vacuo. Medium pressure chromatography eluting with 40% ethyl acetate/hexane afforded the title compound as a white solid (1.5 g, 90%). 1H NMR (360 MHz, d6 -DMSO) δ 3.88 (3H, s), 7.20 (1H, dd, J 2.7 Hz, J 8.8 Hz), 7.51 (1H, d, J 2.7 Hz), 7.68 (1H, d, J 8.8 Hz), 9.83 (1H, s).

Workup

temperatureheated at 75° C. for 1 hour
customreaction
temperatureheated at 75° C. for a further 3 hours
extractionextracted into ethyl acetate (3×70 ml)
washThe combined organics were washed with brine (100 ml)
dry with materialdried over magnesium sulphate
customthe solvent removed in vacuo
washMedium pressure chromatography eluting with 40% ethyl acetate/hexane

Sources & evidence

ORD record: ord-21fc0155849645789f22fe95d9a69295
Source dataset: uspto-grants-2000_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06046195

Reaction notes

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