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

HRID 1865190

반응식

HRID 1865190 반응식
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[CH2:5]2.ClCCCl.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].N[N:31]1[C:39]2[C:34](=[CH:35][CH:36]=C[CH:38]=2)[CH2:33][C:32]1=O>C(N1CCC(=O)CC1)C.CO.C(O)(=O)C>[CH2:39]([N:31]1[CH2:36][CH2:35][CH:34]([NH:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][C:6](=[O:11])[CH2:5]3)[CH2:33][CH2:32]1)[CH3:38]

참가 물질

8

반응물 4

HCID 111,2-DichloroethaneHCID 27732135-Amino-2-oxindoleHCID 37753661-amino-1,3-dihydro-2H-indol-2-oneHCID 5049666Sodium triacetoxyborohydride

생성물 1

HCID 579761065-(1-Ethyl-piperidin-4-ylamino)-1,3-dihydro-indol-2-one수율 58%

시약·촉매·용매 3

HCID 771591-Ethylpiperidin-4-one촉매HCID 176Acetic Acid용매HCID 887Methanol용매

반응 조건

온도
0 °C

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-ab7da183daed4503b1d68e89ba481158
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07626031B2

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