Chloroacetic Acid → 4-(3-{1-Benzhydryl-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 Steps

4.91 g (10.0 mmol, 1 eq) 2-[2-(1-Benzhydryl-5-chloro-1H-indol-2-yl)-ethyl]-isoindole-1,3-dione made according to Example 3 was suspended in 50 mL CH2Cl2. 3.50 g (30.0 mmol, 3 eq) triethylsilane, 2.47 g (12 mmol, 1.2 eq) 4-(3-Oxo-propyl)-benzoic acid ethyl ester and chloro-acetic acid 7.56 g (80 mmol, 8 eq) were added in one portion. The mixture was heated to reflux for 92 h. LC showed less then 2% starting material at this end point. 15 mL sat. aq. NaHCO3 and 10 mL water was added to the reaction mixture, and stirring was continued over a period of 16 h. 10 mL MeOH was then added and the solid was collected by filtration. 9.4 g off-white solid was dried in the oven for 3 h at 60° C. to give 6.12 g 4-(3-{1-Benzhydryl-5-chloro-2-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-1H-indol-3-yl}-propyl)-benzoic acid ethyl ester (90% yield) with 74% purity.

Provenance & Evidence