Carbon Dioxide → 2-(1-Benzyl-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-N,N-dimethyl-acetamide

HRID 71042ノート

反応式

HRID 71042 の反応式
[CH2:1]([N:8]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:11](=[O:12])[C:9]1=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:19]([OH:25])(=O)[CH2:20]C(O)=O.[N:26]1[CH:31]=CC=C[CH:27]=1.C(=O)=O.C(N(CC)CC)C.CN(C)C(Cl)=O>C(OCC)(=O)C>[CH2:1]([N:8]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:11]([CH2:20][C:19]([N:26]([CH3:31])[CH3:27])=[O:25])([OH:12])[C:9]1=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

8

反応物 6

HCID 280Carbon Dioxide2 回HCID 867Malonic AcidHCID 1049PyridineHCID 6598Dimethylcarbamoyl ChlorideHCID 8471TriethylamineHCID 2647341-Benzylisatin

生成物 1

HCID 104039792-(1-Benzyl-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-N,N-dimethyl-acetamide

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

A 500 mL flask is charged with N-benzyl isatin (55 g, 0.231 mol), malonic acid (28.95 g, 0.278 mol), and pyridine (73.4 g, 0.927 mol). To the formed red suspension, ethyl acetate (50 mL) is added, and the stirred mixture is heated to 80° C. After about 30 minutes a solution has formed which is kept stirring at 80° C. until no further formation of carbon dioxide is observed (about 2.5 h). Then triethyl amine (35.2 g, 0.347 mol) is added, and the mixture is stirred for another 10 minutes at 80° C. To the dark red solution, then dropwise (exothermicl) dimethyl carbamoyl chloride (32.4 g, 0.301 mol) is added during 10 minutes. When the evolution of carbon dioxide ceases, the mixture is kept stirring at 80° C. for another two hours, and then the solvent is removed from the brown suspension on the rotavapor. To the residue, HCl (4N, 0.2 L) is added, and the formed suspension is stirred for one hour at 80° C. After cooling and standing in the refrigerator over night, the crystals are filtered off, washed twice with water (about 150 mL each wash) and dried in vacuo to give light brown crystals. Yield of the title compound: 66.7 g (88.7% based on N-benzyl isatin). 1H-NMR (CDCl3, 300 MHz) δ 2.69, 3.03 (AB, 2H, 2J=16.1Hz, CH2CONMe2); 2.91, 2.99 (2 s, 3 each, N(CH3)2); 4.87, 4.89 (AB, 2H, 2J=15.8 Hz, CH2Ph); 6.70 (d, 1H, J=7.7 Hz, H-7); 7.01 (dtr, J=7.7 Hz, J=1.1Hz, H-5); 7.17 (dtr, 1H, J=7.7 Hz, J=1.1Hz, H-6); 7.21-7.34 (m, 5H, Ph); 7.49 (dd, J=7.3 Hz, J=1.8 Hz, H-4). 13C-NMR (CDCl3, 75 MHz) δ 35.64, 37.66 N(CH3)2; 38.21 (CH2CONMe2); 44.02 (CH2Ph); 74.61 (C-3); 109.70 (C-7); 123.38 (C-5); 124.63 (C-4); 127.51, 127.90, 129.03 (Ph ortho-C, para-C, meta-C); 129.82 (C-6), 131.15 (C-9); 135.77 (Ph ipso-C); 142.47 (C-8); 171.18 (CONMe2); 176.51 (C-2).

後処理

  1. customAfter about 30 minutes a solution has formed which
  2. custom(about 2.5 h)
  3. customthe solvent is removed from the brown suspension on the rotavapor
  4. additionTo the residue, HCl (4N, 0.2 L) is added
  5. stirringthe formed suspension is stirred for one hour at 80° C
  6. temperatureAfter cooling
  7. waitstanding in the refrigerator over night
  8. filtrationthe crystals are filtered off
  9. washwashed twice with water (about 150 mL each wash)
  10. customdried in vacuo
  11. customto give light brown crystals

出典と根拠

ORDレコード
ord-2e538e4c9e68404493defb32ab061180
出典データセット
uspto-grants-2014_09
特許番号
US08822702B2

反応ノート

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