1,2-Dichloroethane → 5-(1-Ethyl-piperidin-4-ylamino)-1,3-dihydro-indol-2-one

Participants

Reaction Conditions

Reaction Steps

To a 2 L round bottom flask was added 5-aminooxindole (80 g, 0.54 mol), 1,2-dichloroethane (800 ml), 1-ethyl-4-piperidone (80.1 ml, 0.59 mmol) and Glacial acetic acid (80 ml). The mixture was stirred for 30 minutes, cooled under ice/water bath for 30 minutes and then sodium triacetoxyborohydride (160 g, 0.76 mmol) was added in 10 portions over 60 minutes. The mixture was stirred at room temperature 4 hs. TLC showed no trace of amino-oxindole and then Celite (100 g) and MeOH (500 mL) were slowly added. The reaction mixture was filtered and concentrated. The resulting dark oil was acidified with c-HCl (150 mL) and ice (50 g). The reaction mixture was extracted with ethyl acetate (2 L×2) to remove the side product. The aqueous layer was cooled to 0° C., basified with 40% NaOH (ca. 150 mL) and then the solid was formed. After 30 min stirring, the formed solid was filtered and washed with H2O (1 L) and suspended with Acetone (2 L) for 1 h. After filtering, the crude solid was dissolved in CHCl3 (2.5 L), treated with charcoal (50 g) and filtered using Celite. The filterate was concentrated and solidified with ethyl acetate to give the desired product (81 g, 58%).

Provenance & Evidence