Potassium Iodide → 5-{(3,5-Difluoro-4-hydroxybenzyl)-[2-(5-fluoro-2-{[4'-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]amino}pentanoic acid

HRID 1921904Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1921904
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][CH:27]=3)=[CH:22][CH:21]=2)=[C:6]([CH2:8][CH2:9][NH:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16])[CH:7]=1.Br[CH2:37][C:38]1[CH:39]=[C:40]([F:56])[C:41]([O:45][Si](C(C)C)(C(C)C)C(C)C)=[C:42]([F:44])[CH:43]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CC(C)=O.C(OCC)(=O)C.O>[F:44][C:42]1[CH:43]=[C:38]([CH:39]=[C:40]([F:56])[C:41]=1[OH:45])[CH2:37][N:10]([CH2:9][CH2:8][C:6]1[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=1[O:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:27]=[CH:28][C:29]([C:32]([F:33])([F:34])[F:35])=[CH:30][CH:31]=2)=[CH:22][CH:21]=1)[CH2:11][CH2:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16]

Komponenten

8

Edukt 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 579719075-{[2-(5-Fluoro-2-{[4'-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]amino}pentanoic acidHCID 579719463,5-Difluoro-4-triisopropylsilanyloxybenzyl bromide

Produkt 1

HCID 162256195-{(3,5-Difluoro-4-hydroxybenzyl)-[2-(5-fluoro-2-{[4'-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]amino}pentanoic acid

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 180AcetoneLösungsmittelHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A solution of 40 mg (0.08 mmol) of 5-{[2-(5-fluoro-2-{[4′-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]amino}pentanoic acid in 5 ml of acetone is mixed with 54.5 mg (0.09 mmol) of [4-(bromomethyl)-2,6-difluorophenoxy]triisopropyl)silane (Example 16A), 22.6 mg (0.16 mmol) of potassium carbonate and 20.3 mg (0.12 mmol) of potassium iodide and heated under reflux for 12 h. Cooling is followed by addition of water to the mixture and extraction with ethyl acetate. The organic phase is washed with saturated sodium chloride solution, dried over magnesium sulfate and the solvent is distilled off in vacuo. The resulting residue is purified by preparative HPLC. 15.3 mg (0.024 mmol, 30% of theory) of the title compound are obtained.

Aufarbeitung

  1. temperatureheated
  2. temperatureunder reflux for 12 h
  3. temperatureCooling
  4. washThe organic phase is washed with saturated sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. distillationthe solvent is distilled off in vacuo
  7. customThe resulting residue is purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-5180db99d776428e94f1ec8d03af9976
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08173704B2

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