3-(Boc-aMinoMethyl)-4-fluorobenzeneboronic acid pinacol ester, 96% synthesis

Yield:1035391-48-0 84%

Reaction Conditions:

with potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride in 1,4-dioxane at 22; for 1.66667 h;Heating / reflux;

Steps:

113.113A

EXAMPLE 113; 4-(4-(3-(aminomethyl)-4-fluorophenyl)-lH-benzordlimidazol-2-yl)-l-(7H-pyrrolor2,3- dlpyrimidin-4-yl)piperidin-4-amine113A. tert-butyl 2-fluoro-5-(4A5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)benzylcarbamateBis(pinacolato)diboron (2.83 g, 11.13 mmol), tert-butyl 5-bromo-2-fluorobenzylcarbamate (2.82 g, 9.27 mmol) (CAS no. 491836-84-1, prepared by a method very similar to that described in WO 2005094822) and potassium acetate (4.55 g, 46.36 mmol) were suspended in 1,4-dioxane (25 mL) at 22 ⁰C under nitrogen. A stream of nitrogen was passed through the mixture for 10 minutes. l,r-Bis(diphenylphosphino)ferrocene- palladium dichloride (0.191 g, 0.23 mmol) was added and the mixture was heated at reflux for 1.5 hours. The mixture was concentrated and the residue was treated with DCM (500 mL). The insoluble material was removed by filtration through a plug of silica. The silica was washed through with further DCM. The combined filtrates were concentrated and the residue purified by flash silica chromatography, eluting with 10 to 30% ethyl acetate in isohexane. Pure fractions were evaporated to dryness to afford tert-butyl 2-fluoro-5- (4,4,5, 5-tetramethyl-l,3,2-dioxaborolan-2-yl)benzylcarbamate (2.74 g, 84 %) as a colourless gum.¹R NMR (399.9 MHz, CDCl₃) δ 1.33 (12H, s), 1.46 (9H, s), 4.37 (2H, s), 4.83 (IH, s), 7.00 - 7.05 (IH, m), 7.68 - 7.72 (IH, m), 7.77 (IH, d). M/z : [M+H-C₄H₈]+ 296

References:

WO2008/75109,2008,A1 Location in patent:Page/Page column 232-233