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

온도

0 °C

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%).

1. temperaturecooled under ice/water bath for 30 minutes
2. stirringThe mixture was stirred at room temperature 4 hs
3. filtrationThe reaction mixture was filtered
4. concentrationconcentrated
5. extractionThe reaction mixture was extracted with ethyl acetate (2 L×2)
6. customto remove the side product
7. customthe solid was formed
8. stirringAfter 30 min stirring
9. filtrationthe formed solid was filtered
10. washwashed with H2O (1 L)
11. waitsuspended with Acetone (2 L) for 1 h
12. filtrationAfter filtering
13. dissolutionthe crude solid was dissolved in CHCl3 (2.5 L)
14. additiontreated with charcoal (50 g)
15. filtrationfiltered
16. concentrationThe filterate was concentrated

ORD 기록

ord-ab7da183daed4503b1d68e89ba481158

출처 데이터셋

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07626031B2