2-methyl-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole synthesis

Yield:955979-22-3 69%

Reaction Conditions:

with (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride;potassium acetate in 1,4-dioxane at 90;

Steps:

55 Intermediate 552-Methyl-4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-indole

To a suspension of 2-methyl-4-bromoindole (970 mg, 4.62 mmol),bispinacolatodiboron (1.29 g, 5.08 mmol, 1.1 eq), KOAc (1.36 g, 13.9 mmol, 3eq) in dioxane (30 mL) was added PdCl2dppf (101 mg, 0.14 mmol, 0.03 eq) under Ar(g). The reaction mixture was heated up to 9000 overnight. It was then cooled down to rt, partitioned with water (40 mL) and extracted with EtOAc (3 x 50 mL). The combined organics were dried over MgSO4, filtered and the solventwas removed in vacuo. Purification by silica gel column chromatography withhexane/EtOAc (1:0-1:1) yielded Intermediate 55 as a pale yellow solid (850 mg,69%).1H NMR (300MHz, DMSO-d5) oH. 10.88 (brs, 1H), 7.27-7.40 (m, 2H), 6.90-7.02(m, 1H), 6.43 (d, J=0.9 Hz, 1H), 2.39 (5, 3H), 1.31 (5, 12H).MS (ESj 258.2 (100%, [M+H]j.

References:

WO2017/29521,2017,A1 Location in patent:Page/Page column 63