5-Amino-2-chloro-4-methyl-benzoic acid methyl ester synthesis

Yield:1143026-47-4 71%

Reaction Conditions:

with potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride in 1,4-dioxane;water at 110; for 18 h;

Steps:

6.F.2 (5-Amino-2-chloro-4-methyl-phenyl)-tert-butyl-dimethylsilyl-methanol

Step 2 5-Amino-2-chloro-4-methyl-benzoic acid methyl ester To a solution of 5-amino-6-bromo-2-chloro-benzoic acid methyl ester (0.5 g, 1.89 mmol) in dioxane (10 ml) and water (1 ml) was added potassium carbonate (0.784 g, 5.67 mmol), PdCl₂(dppf) (0.54 g, 0.189 mmol) and trimethyl boroxine (0.276 ml, 1.985 mmol). The mixture was stirred at 110° C. for 18 hours, then cooled to room temperature and filtered. The filtrate was concentrated to dryness under reduced pressure. Purification of the residue by flash chromatography (hexanes:EtOAc 8:2) gave 0.270 g (71%) of 5-amino-2-chloro-4-methyl-benzoic acid methyl ester as a tan solid.

References:

US2010/160389,2010,A1 Location in patent:Page/Page column 49