Ethyl orthoformate → 1-[2-methoxy-5-(1H-tetrazol-1-y1)phenyl]ethanone

HRID 1870232Notes

Reaction equation

[CH:1](OCC)(OCC)OCC.[NH2:11][C:12]1[CH:13]=[CH:14][C:15]([O:21][CH3:22])=[C:16]([C:18](=[O:20])[CH3:19])[CH:17]=1.[N-:23]=[N+:24]=[N-:25].[Na+]>C(O)(=O)C>[CH3:22][O:21][C:15]1[CH:14]=[CH:13][C:12]([N:11]2[CH:1]=[N:25][N:24]=[N:23]2)=[CH:17][C:16]=1[C:18](=[O:20])[CH3:19]

Participants

Conditions

Temperature: 75 °C

Procedure

Triethyl orthoformate (28.79 ml, 25.65 g, 173 mmol) was added to a stirred, heated (80° C.) solution of 1-(5-amino-2-methoxyphenyl)ethanone (8.16 g, 49 mmol) in acetic acid (80 ml) and the mixture was stirred at 75° C. for 1 hour. Sodium azide (9.64 g, 148 mmol) was added in portions over 90 minutes, then the mixture was stirred at 75° C. for 4 hours. The mixture was cooled to room temperature and the solvent was evaporated under reduced pressure. Hydrochloric acid (1M, 100 ml) was added and the mixture was stirred at room temperature 1 hour. The solid was collected, flushed with toluene (100 ml) and dried in vacuo at room temperature. The residue was recrystallized from ethanol (700 ml) to give 1-[2-methoxy-5-(1H-tetrazol-1-y1)phenyl]ethanone as tan coloured needles (7.88 g, 73%), 1H NMR (d6 -DMSO) δ 10.06 (1H, s), 8.06 (2H, m), 7.46 (1H, d, J=7.8 Hz), 3.99 (3H, s), and 2.60 (3H, s). m/e (CI+) 219 (MH+)

Workup

stirringthe mixture was stirred at 75° C. for 4 hours
temperatureThe mixture was cooled to room temperature
customthe solvent was evaporated under reduced pressure
additionHydrochloric acid (1M, 100 ml) was added
stirringthe mixture was stirred at room temperature 1 hour
customThe solid was collected
customflushed with toluene (100 ml)
customdried in vacuo at room temperature
customThe residue was recrystallized from ethanol (700 ml)

Sources & evidence

ORD record: ord-25148099c37041d88647cecea2cc2f51
Source dataset: uspto-grants-2000_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06096766

Reaction notes

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