4-Bromo-2-methylaniline → 3-[(4-Bromo-2-methylphenyl)amino]isonicotinic acid

HRID 78761

Reaction equation

[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([CH3:9])[CH:3]=1.F[C:11]1[CH:12]=[N:13][CH:14]=[CH:15][C:16]=1[C:17]([OH:19])=[O:18].[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:15]2[CH:14]=[N:13][CH:12]=[CH:11][C:16]=2[C:17]([OH:19])=[O:18])=[C:4]([CH3:9])[CH:3]=1

Participants

Conditions

Temperature: -78 °C

Procedure

4-Bromo-2-methylaniline (186 mg, 1.00 mmol) and 3-fluoropyridine-4-carboxylic acid (141 mg, 1.00 mmol) were dissolved in dry THF (6.0 ml) under argon and the mixture was cooled to −78° C. A solution of LiHMDS (1.0M in THF, 3.5 ml) was added and the reaction mixture was allowed to warm to ambient temperature. After 24 h the reaction was quenched by adding a solution of HCl in dioxane (4.0M, 2.0 ml). The volatiles were removed in vacuo and the crude material was purified by flash chromatography using silica gel and a gradient of 0-10% methanol in DCM as eluent to give 215 mg (701 μmol; 70% yield) of pure desired product.

Workup

temperatureto warm to ambient temperature
customAfter 24 h the reaction was quenched
additionby adding a solution of HCl in dioxane (4.0M, 2.0 ml)
customThe volatiles were removed in vacuo
customthe crude material was purified by flash chromatography

Sources & evidence

ORD record: ord-c43d7ea710e345ed992807a60eabeb95
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08841459B2

Linked notes

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