Trifluoroacetic acid → 4-(2-{5-Chloro-2-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-1H-indol-3-yl}-ethoxy)-benzoic Acid Methyl Ester

Participants

Reaction Conditions

Reaction Steps

To a solution 4-(2,2-diethoxy-ethoxy)-benzoic acid methyl ester (495 g, 1.84 mol), triethylsilane ((536 g, 4.62 mol) and 2-[2-(5-chloro-1 H-indol-2-yl)-ethyl]-isoindole-1,3-dione (500 g, 1.54 mol) in dichloromethane (3.5 L) was added trifloroacetic acid (878 g, 7.7 mol) during a period of 1 hour. Then, the reaction mixture was cooled to 0-10° C. A mixture of triethyl amine (787 g) and methanol (4 L) was added during a period of 45 min. The reaction mixture was stirred for 1 h at 0-10° C. and filtered. The crude product was washed with methanol (2×1000 mL) and dried to give a white solid (483 g) in 62% yields and 88.1% area purity. 1H NMR (CDCl3): δ6.9-8.6 (m, Ph, CHPh2), 4.13 (t, 2H, J=6.6 Hz), 4.04 (t, 2H, J=7.2 Hz), 4.13 (t, 2H, J=6.6 Hz), 3.87 (S, 3H), 3.23 (t, 2H, J=7.2 Hz), 3.16 (t, 2H, J=6.6 Hz).

Provenance & Evidence