Ethyl Acetate → 6-bromo-2-methoxy-3-(4-methyl-1H-imidazol-1-yl)pyridine

HRID 475720Notes

Reaction equation

[Br:1][C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([N:10]([CH2:13][C:14](=O)[CH3:15])[CH:11]=O)=[CH:4][CH:3]=1.C([O-])(=O)C.[NH4+:21].C(OCC)(=O)C.[OH-].[Na+]>C(O)(=O)C>[Br:1][C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([N:10]2[CH:13]=[C:14]([CH3:15])[N:21]=[CH:11]2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 140 °C

Procedure

A mixture of N-(6-bromo-2-methoxypyridin-3-yl)-N-(2-oxopropyl)formamide (7072 mg, 24.63 mmol) and ammonium acetate (8714 mg, 113 mmol) in 16 mL of acetic acid was heated at 140° C. for 1 h. The reaction mixture was cooled to rt and poured into a mixture of icewater and ethyl acetate. The pH of the resulting mixture was brought to pH 9 with a 50% aqueous sodium hydroxide solution. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate and filtered. The solvent was removed in vacuum and the residue was purified by column chromatography on silica gel to give 6-bromo-2-methoxy-3-(4-methyl-1H-imidazol-1-yl)pyridine (959.0 mg, 3.58 mmol, 14.52% yield) as brown solid. LC-MS (M+H)+=270.0.

Workup

temperatureThe reaction mixture was cooled to rt
customThe organic layer was separated
extractionthe aqueous layer was extracted with ethyl acetate
dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
filtrationfiltered
customThe solvent was removed in vacuum
customthe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record: ord-ebe1c305f8f14f3998a4b469b659e0a1
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637525B2

Reaction notes

Loading…