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

HRID 324106

Reaction equation

HRID 324106 reaction equation
[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

Participants

7

Reactant 4

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

Product 1

HCID 22237625N-(8-indol-1-yl-octyl)-3,5-bis(3-chlorophenyl)4-hydroxybenzamideYield 3,976.5%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
66 °C

Procedure

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) δ1.24 (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)+.

Workup

  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)

Sources & evidence

ORD record
ord-2a72dc4a8bb44ef6993046145a7888b7
Source dataset
uspto-grants-2001_04
Patent number
US06214877B1

Linked notes

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