2-amino-4-bromo-3-methylphenol synthesis

Yield:1154740-46-1 100%

Reaction Conditions:

Stage #1: 4-bromo-3-methyl-2-nitro-phenolwith tin(ll) chloride in ethanol; for 3.5 h;Heating / reflux;
Stage #2: with sodium hydrogencarbonate in ethanol;water; pH=~ 7.5;

Steps:

5.2

Step 2:To a well stirred ethanol solution (75 mL) of 5b (8.1 g, 34.9 mmol), SnCI₂ (20 g, 105 mmol) is added. The reaction mixture is stirred at reflux for 2.5 h. After that period, the transformation is incomplete, therefore, more SnCI₂ (2g, 10 mmol) is added and the reaction mixture is heated at reflux for 1 h before being cooled to RT. The mixture is poured onto 250 g of ice and the pH adjusted to approximately 7.5 with aqueous 5% NaHCO₃. The product is extracted with EtOAc (3 X 100 mL) before being washed with saturated brine (2 X 100 mL). The organic phase is dried over anhydrous MgSO₄, filtered and concentrated to dryness to give the aniline intermediate 5c as a gray solid (8.25 g, ~100% yield; this material contained some tin residues, nonetheless, it is used as such for the following step).

References:

WO2009/62285,2009,A1 Location in patent:Page/Page column 54-55