Sodium hydride → {2-[3,3''-Dichloro-5'-(8-indol-1-yl-octylcarbamoyl)-[1,1':3',1'']terphenyl-2'-yloxy]-ethoxy}acetic acid, methyl ester

HRID 1743488

Reaktionsgleichung

Reaktionsgleichung von HRID 1743488
[N:1]1([CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19](=[O:44])[C:20]2[CH:25]=[C:24]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[CH:27]=3)[C:23]([O:33][CH2:34][CH2:35][OH:36])=[C:22]([C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([Cl:43])[CH:38]=3)[CH:21]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[H-].[Na+].[CH3:47][O:48][C:49](=[O:52])[CH2:50]Br.C1OCCOCCOCCOCCOC1>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:32][C:28]1[CH:27]=[C:26]([C:24]2[CH:25]=[C:20]([C:19](=[O:44])[NH:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][N:1]3[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[CH:3]=[CH:2]3)[CH:21]=[C:22]([C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([Cl:43])[CH:38]=3)[C:23]=2[O:33][CH2:34][CH2:35][O:36][CH2:50][C:49]([O:48][CH3:47])=[O:52])[CH:31]=[CH:30][CH:29]=1

Komponenten

7

Edukt 4

HCID 24758Sodium hydrideHCID 3633615-Crown-5HCID 60984Methyl bromoacetateHCID 22237401N-(8-indol-1-yl-octyl)-3,5-bis(3-chlorophenyl)-4-(2-hydroxyethoxy)benzamide

Produkt 1

HCID 86583669{2-[3,3''-Dichloro-5'-(8-indol-1-yl-octylcarbamoyl)-[1,1':3',1'']terphenyl-2'-yloxy]-ethoxy}acetic acid, methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 67553Tetrabutylammonium IodideKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a stirred solution of N-(8-indol-1-yl-octyl)-3,5-bis(3-chlorophenyl)-4-(2-hydroxyethoxy)benzamide (0.629 g, 1 mmol) in THF (10 ml) under nitrogen at room temperature was sodium hydride (0.055 g, 2.3 mmol). The mixture was refluxed for 45 minutes, cooled and methylbromoacetate (0.189 g, 1.2 mmol), 15-crown-5 ether (0.022 g, 0.1 mmol), and tetrabutylammoniumiodide (0.037 g, 0.1 mmol) were added. The mixture was refluxed. After 6 h, the reaction mixture was quenched with water and then diluted with water (100 ml) and extracted with EtOAc. This gave a thick emulsion which was separated by acidfying the mixture with 1N HCl. The combined extracts were washed with water (2×15 ml), brine (2×15 ml), dried over Na2SO4, filtered and the filtrate concentrated in vac and dried. The residue was purified by flash chromatography (15%, 20% EtOAc/Hex) and then preparatory plate chromatography (50% EtOAc/Hex) to give the desired product as a viscous, hazy oil (0.400 g, 57%); 1H NMR (400 MHz, DMSO-d6) δ 1.16–1.31 (m, 8H), 1.45–1.53 (m, 2H), 1.68–1.76 (m, 2H), 3.20–3.26 (m, 4H), 3.45–3.48 (m, 2H), 3.58 (s, 3H), 3.71 (s, 2H), 4.12 (t, J=6.8 Hz, 2H), 6.37 (dd, J=0.8, 3.1 Hz, 1H), 6.95–6.99 (m, 1H), 7.06–7.10 (m, 1H), 7.32 (d, J=3.1 Hz, 1H), 7.40–7.52 (m, 6H), 7.57–7.60 (m, 2H), 7.67–7.70 (m, 2H), 7.87 (s, 2H), 8.52 (t, J=4.83 Hz, 1H); IR (film) 3300, 2800, 1750, 1630, 1540, 1470, 1220 cm−1; mass spectrum [(+)APCI], m/z 701 (M+H)+.

Aufarbeitung

  1. customat room temperature
  2. temperatureThe mixture was refluxed for 45 minutes
  3. temperaturecooled
  4. temperatureThe mixture was refluxed
  5. customthe reaction mixture was quenched with water
  6. additiondiluted with water (100 ml)
  7. extractionextracted with EtOAc
  8. customThis gave a thick emulsion which
  9. customwas separated
  10. washThe combined extracts were washed with water (2×15 ml), brine (2×15 ml)
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationthe filtrate concentrated in vac
  14. customdried
  15. customThe residue was purified by flash chromatography (15%, 20% EtOAc/Hex)

Quellen und Nachweise

ORD-Eintrag
ord-d6824f393ccc462781447b8c720d47b5
Quelldatensatz
uspto-grants-2006_03
Patentnummer
US07008636B2

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