3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline synthesis

Yield:1312535-18-4 88%

Reaction Conditions:

with anhydrous potassium acetate;dicyclohexyl(2’,4’,6’-triisopropyl-[ 1,1’-bi-phenyl]-2-yl)phosphane;tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ in 1,4-dioxane at 20 - 80; for 4 h;Inert atmosphere;

Steps:

Dioxane (720 mL) in a 1 L three-necked round bottom flask was degassed for 30 min. 3-Bromo-5-methylaniline (60g, 193 mmol), (bispinacolato)diboron (96 g, 377 mmol), potassium acetate (42.7 g, 435 mmol), X-Phos (8.3 g, 17.41 mmol) and Pd₂dba₃ (3.99 g, 4.35 mmol) were added to the degassed solvent under N₂(g). After Stirling for 10 min at room temperature, the system was heated to an internal temperature of 80 °C. After ca. 4 hours, the heating mantle was removed and replaced with an ice water bath. The reaction mixture was cooled to 30 °C, and was then filtered through a pad of celite (washing with 500 mL of MTBE). This was transferred to a 4 L separatory funnel containing 500 mL pH 8 phosphate buffer, 500 mL brine, and an additional 500 mL of MTBE. The layers were cut and the organic washed with 1 L of a 1 : 1 mixture of brine and water. The aqueous layers were combined and were sequentially back extracted with a second 500 mL portion of MTBE. The combined organics were treated with 100 g of MgS0₄ and the resulting mixture stirred for 20 min. This was then filtered and concentrated in vacuo. The resultant residue was purified by flash chromatography (Biotage, 0-25% ethyl acetate in hexanes) to yield 3-methyl-5-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)aniline (66 g, 255 mmol, 88%) as a light orange solid. MS APCI: [M + H]⁺ /z 234.2.

References:

WO2011/75560,2011,A1 Location in patent:Page/Page column 30