1,4-Dioxane → 4-Cyano-3-(3-methyl-isoquinolin-4-yl)-benzoic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

Into a 40 mL screw-top vial with a stirbar was added 3 (500 mg, 2.25 mmol), 4-cyano-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester (776 mg, 2.70 mmol, 1.2 eq) (prepared according to procedure in J. Am. Chem. Soc., 127, 10539, (2005)), and K3PO4 (1.004 g, 4.73 mmol. 2.1 eq) in a 10:1 mixture of 1,4-dioxane:H2O (10 mL/1 mL). To the solution was added bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (31.9 mg, 2 mol %), the vial capped and the contents heated to 100° C. for 4 hrs. The reaction was cooled to room temperature and diluted with ethyl acetate (100 mL). The solid was filtered and the filtrate washed with water (2×30 mL), brine, followed by drying over Na2SO4, and concentrating to a yellow oil. The crude product was purified using Biotage MPLC system (25S column size, 0-30% ethyl acetate/heptane, over 30CV, then 30% isocratic for 10CV) giving white solid as the product (455 mg, 1.51 mmol, 67%). 1H NMR (CDCl3, 400 MHz): δ 9.34 (s, 1H), δ 8.30-8.27 (dd, 1H), δ 8.13 (s, 1H), δ 8.08-8.05 (m, 1H), δ 8.00-7.98 (d, 1H), δ 7.64-7.61 (m, 2H), δ 7.17-7.15 (m, 1H), δ 3.99 (s, 1H), δ 2.51 (s, 3H); LRMS (m/z): 303 (M+H)

Provenance & Evidence