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

Participants

Reaction Conditions

Reaction Steps

To a solution 4-(3-oxo-propyl)-)-benzoic acid ethyl ester (381 g, 1.85 mol), triethylsilane ((537 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 (4 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 (778 g) and methanol (3 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 (313 g) in 50% yield. 1H NMR (CDCl3): δ6.9-8.2 (m, Ph, CHPh2), 4.35 (dd, 2H, J=14.3 Hz, 7.2 Hz), 3.99 (t, 2H, J=7.1 Hz), 3.13 (t, 2H, J=7.2 Hz), 2.69 (t, 4H, J=7.3 Hz) 1.90 (m, 2H), 1.38 (t, 3H, J=7.1 Hz).

Provenance & Evidence