2,5-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenamine synthesis

Yield:939807-75-7 85%

Reaction Conditions:

with tris(dibenzylideneacetone)dipalladium⁽⁰⁾ chloroform complex;potassium acetate;tricyclohexylphosphine in 1,4-dioxane at 120;

Steps:

36.1 Step 1: 2,5-Difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline

A flask was charged with Pd₂(dba)₃.CHCl₃ (45 mg, 0.04 mmol) and tricyclohex- ylphosphine (55 mg, 0.20 mmol). Degased 1,4-Dioxane (10 mL) was added and the resulting mixture was stirred 25 minutes at rt before addition of bis(pinacolato)diboron (700 mg, 2.76 mmol), potassium acetate (715 mg, 7.21 mmol) and 4-Bromo-2,5-difluoroaniline (500 mg, 2.40 mmol) in that order. The reaction mixture was stirred overnight at 120 ^oC then diluted with EtOAc, filtered through a pad of celite and concentrated under reduced pressure. The crude material was purified by flash chromatography through silica gel (0 - 100% (0994) CH2Cl2/heptanes) to provide the title compound (524 mg, 85% yield). LCMS (ESI) [M+H]⁺ = 256.3.

References:

WO2020/172093,2020,A1 Location in patent:Paragraph 0700-0701