Trimethylsilyldiazomethane → 2-(4-Bromo-2-fluorophenylamino)-6-chloro-nicotinic acid methyl ester
Reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:10]=2[C:11]([OH:13])=[O:12])=[C:4]([F:19])[CH:3]=1.[CH3:20][Si](C=[N+]=[N-])(C)C>CO.C1C=CC=CC=1>[CH3:20][O:12][C:11](=[O:13])[C:10]1[CH:14]=[CH:15][C:16]([Cl:18])=[N:17][C:9]=1[NH:8][C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=1[F:19]Participants
Procedure
To a suspension of 2-(4-bromo-2-fluorophenylamino)-6-chloro-nicotinic acid (5.00 g, 14.5 mmol) in methanol/benzene (1:1, 100 mL) under N2 was added (trimethylsilyl)diazomethane (2.0 M solution in hexanes) dropwise until the bubbling caused by gas evolution ceased. Solids precipitated out of solution. The reaction was allowed to stir for 1 hour. Excess (trimethylsilyl)diazomethane was quenched by the dropwise addition of glacial acetic acid. The precipitated solids were filtered and washed with methanol. The filtrate was concentrated to a smaller volume and additional solids precipitated out of solution that were filtered and washed with methanol. The solids were combined and dried under vacuum to yield 4.82 g (93%) of pure desired product as a dark pink solid.
Workup
- customSolids precipitated out of solution
- customExcess (trimethylsilyl)diazomethane was quenched by the dropwise addition of glacial acetic acid
- filtrationThe precipitated solids were filtered
- washwashed with methanol
- concentrationThe filtrate was concentrated to a smaller volume and additional solids
- customprecipitated out of solution that
- filtrationwere filtered
- washwashed with methanol
- customdried under vacuum
Sources & evidence
- ORD record
- ord-cc30c849572042078f5f238e9e5ebaa4
- Source dataset
- uspto-grants-2013_04
- Patent number
- US08431574B2
Reaction notes
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