Water → 2-amino-5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-N-methylbenzamide

関与物質

反応手順

2-Amino-5-bromo-N-methyl-benzamide (Compound 106A, 645.0 mg, 2.816 mmol), 1,4-dioxaspiro[4,5]dec-7-ene-8-boronic acid pinacol ester (899.2 mg, 3.379 mmol) and [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (229.9 mg, 0.2816 mmol) were added to a 20 mL microwave tube and taken up in 1,4-Dioxane (8 mL, 100 mmol). This mixture was treated with a solution of potassium carbonate (1167 mg, 8.447 mmol) in H2O (3 mL, 200 mmol). After sparging the mixture with N2 for 1 minute, the tube was sealed and irradiated in the Biotage microwave reactor for 30 minutes at 100° C. The mixture was poured into water and extracted twice with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated to a black goo. This was taken up in DCM, treated with silica and concentrated to a plug. This plug was loaded into a sample cartridge and purified on an ISCO Combiflash unit (0-40%-70% EtOAc/Hexane) to isolate the desired product as 359 mg of a white solid. 1H NMR (400 MHz, DMSO-d6) δ 1.78 (t, J=6.44 Hz, 2H), 2.33 (br. s., 2H), 2.50-2.51 (m, J=1.80 Hz, 2H), 2.72 (d, J=4.55 Hz, 3H), 3.91 (s, 4H), 5.85 (t, J=3.92 Hz, 1H), 6.41 (s, 2H), 6.63 (d, J=8.59 Hz, 1H), 7.23 (dd, J=8.59, 2.02 Hz, 1H), 7.48 (d, J=2.27 Hz, 1H), 8.23 (d, J=4.29 Hz, 1H). MS (ES+): m/z=289.06 (100) [M+1]. HPLC: tR=2.62 min (ZQ3, polar—5 min).

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