Dichloromethane → N-(8-indol-1-yl-octyl)-3,5-bis(3-chlorophenyl)4-hydroxybenzamide

HRID 1281426

Reaktionsgleichung

Reaktionsgleichung von HRID 1281426
[N:1]1([CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19](=[O:29])[C:20]2[CH:25]=[C:24](I)[C:23]([OH:27])=[C:22](I)[CH:21]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.C([O-])([O-])=O.[K+].[K+].[Cl:36][C:37]1[CH:38]=[C:39](B(O)O)[CH:40]=[CH:41][CH:42]=1.[CH2:46]([Cl:48])Cl>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[N:1]1([CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19](=[O:29])[C:20]2[CH:25]=[C:24]([C:41]3[CH:40]=[CH:39][CH:38]=[C:37]([Cl:36])[CH:42]=3)[C:23]([OH:27])=[C:22]([C:3]3[CH:4]=[CH:5][CH:6]=[C:46]([Cl:48])[CH:2]=3)[CH:21]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

Komponenten

7

Edukt 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 2734323(3-Chlorophenyl)boronic acidHCID 22237561N-(8-indol-1-yl-octyl)-3,5-diiodo-4-hydroxybenzamide

Produkt 1

HCID 22237625N-(8-indol-1-yl-octyl)-3,5-bis(3-chlorophenyl)4-hydroxybenzamideAusbeute 3.976,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
66 °C

Versuchsvorschrift

A mixture of N-(8-indol-1-yl-octyl)-3,5-diiodo-4-hydroxybenzamide (4.016 g, 6.517 mmol), 2 M K2CO3 (9.8 ml in water), dioxane (100 ml), 3-chlorophenylboronic acid (2.242 g, 14.336 mmol), and [1,1′bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with CH2Cl2 (0.106 g, 0.130 mmol) was warmed to 66° C. After 2 h, the reaction mixture was cooled and concentrated in vac. The residue was taken up in EtOAc (200 ml) and 1N HCl (50 ml). The layers were shaken, separated and the organic layer was washed with 1N HCl (2×50 ml), brine (2×50 ml), dried over Na2SO4, filtered and the filtrate concentrated in vac and dried. The crude product was purified by flash chromatography (alumina, hexane to 60% EtOAc/Hex gradient) to give a light yellow foam (3.027 g, 79%); 1H NMR (300 MHz, DMSO-d6) δ 1.24 (broad s, 8H), 1.43-1.52 (m, 2H), 1.65-1.75 (m, 2H), 3.16-3.26 (q, J=7.5 Hz, 2H), 4.12 (t, J=7.5 Hz, 2H) 6.38 (d, J=3 Hz, 1H), 6.94-7.00 (m, 1H), 7.05-7.13 (m, 1H), 7.33 (d, J=3 Hz, 1H), 7.40-7.53 (m, 8H), 7.62 (s, 2H), 7.76 (s, 2H), 8.40 (t, J=5 Hz, 1H), 9.19 (s, 1H); mass spectrum [(+)ESI], m/z 585 (M+H)+.

Aufarbeitung

  1. temperaturethe reaction mixture was cooled
  2. concentrationconcentrated in vac
  3. customseparated
  4. washthe organic layer was washed with 1N HCl (2×50 ml), brine (2×50 ml)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated in vac
  8. customdried
  9. customThe crude product was purified by flash chromatography (alumina, hexane to 60% EtOAc/Hex gradient)

Quellen und Nachweise

ORD-Eintrag
ord-c843aa3f0f654cedbb88a2033da6f55f
Quelldatensatz
uspto-grants-2002_09
Patentnummer
US06451827B2

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