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

HRID 1865190

反応式

HRID 1865190 の反応式
[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]

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 771591-Ethylpiperidin-4-one触媒HCID 176Acetic Acid溶媒HCID 887Methanol溶媒

反応条件

温度
0 °C

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-ab7da183daed4503b1d68e89ba481158
出典データセット
uspto-grants-2009_12
特許番号
US07626031B2

関連ノート

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