Indole → 2-(6-methoxy-2-naphthyl)-3-pentyl-1H-indole

HRID 392290

반응식

HRID 392290 반응식
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C:13](=O)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[CH:7]=[CH:6]2.[C:21]1([NH:27]N)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.N1C2C(=CC=CC=2)C=C1>C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C:13]1[NH:27][C:21]3[C:26]([C:14]=1[CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH:7]=[CH:6]2

참가 물질

6

반응물 4

HCID 798IndoleHCID 6101p-Toluenesulfonic acidHCID 7516PhenylhydrazineHCID 100617011-(6-Methoxynaphthalen-2-yl)heptan-1-one

생성물 1

HCID 223273422-(6-methoxy-2-naphthyl)-3-pentyl-1H-indole수율 102.6%

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

To a stirred suspension of the 1-(6-methoxy-2-naphthyl)heptan-1-one (81.5 g, 301.44 mmol) in ethanol (2000 mL) under N2 was added phenylhydrazine (35.857 g, 331.58 mmol) and p-toluene sulfonic acid monhydrate (120.41 g, 633.02 mmol). The mixture was refluxed. Warming gave a homogenous solution. (A modification of this Fisher indole reaction to incorporate varied substitution on the indole ring utilizes an N-arylhydrazone in place of the aryl hydrazine-details of hydrazone preparation in a recent JACS, S. Wagaw; B. H. Yang; S. L. Buchwald. JACS, 121, 1999, 10251-10263). After 92 h reflux, heating was stopped and the reaction mixture cooled and rotovap'd to a residue. The residue was partitioned between EtOAc (1700 mL) and 1 N HCl (500 mL). The layers were shaken, separated, and the organic layer washed with 1 N HCl (2×300 mL), sat. aq. NaHCO3 (3×250 mL), H2O (3×250 mL), brine (2×250 mL), dried over Na2SO4, filtered, rotovap'd and dried in vacuo to give a dark viscous oil (106.2 g). The residue was triturated with hexane to give an off-white solid which was collected, rinsed and dried in vacuo to give the product as an off-white solid (95.9 g, 279.21 mmol, 93%) which dec. 93-96° C. 400 mg of the crude indole was recrystallized from hexane to give the product as a white solid (298 mg) with mp 95-97°C.; 1H NMR (DMSO-d6) δ 0.82 (t, J=7.0 Hz, 3H), 1.31 (m, 4H), 1.66 (m, 2H), 2.89 (t, J=7.6 Hz, 2H), 3.90 (s, 3H), 6.98-7.02 (m, 1H), 7.07-7.10 (m, 1H), 7.21 (dd, J=2.4, 8.9 Hz, 1H), 7.34-7.37 (m, 2H), 7.54 (d, J=7.94 Hz, 1H), 7.73 (dd, J=1.5, 8.6 Hz, 1H), 7.88 (d, J=9.00 Hz, 1H), 7.93 (d, J=8.55 Hz, 1H), 8.03 (s, 1H), 11.17 (s, 1H); IR (solid) 3350, 2960, 2920, 2840, 1600, 1200, 740, cm−1; mass spectrum [ESI], m/z 344 (M+H)+;

후처리

  1. temperatureThe mixture was refluxed
  2. temperatureWarming
  3. customgave a homogenous solution
  4. temperatureAfter 92 h reflux
  5. temperatureheating
  6. temperaturethe reaction mixture cooled
  7. customThe residue was partitioned between EtOAc (1700 mL) and 1 N HCl (500 mL)
  8. customseparated
  9. washthe organic layer washed with 1 N HCl (2×300 mL), sat. aq. NaHCO3 (3×250 mL), H2O (3×250 mL), brine (2×250 mL)
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. customdried in vacuo

출처 및 근거

ORD 기록
ord-b6160314d50746d7b1932109c07d79c5
출처 데이터셋
uspto-grants-2004_10
특허 번호
US06800654B2

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