Cesium fluoride → 4'-{2-[(1S,2R)-2-Hydroxy-2-(4-hydroxyphenyl)-1-methylethylamino]ethoxy}-2,3',5'-trimethylbiphenyl-4-carboxylic acid

HRID 30770

Reaktionsgleichung

Reaktionsgleichung von HRID 30770
[CH3:1][C:2]1[CH:22]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:20]=[C:19]([CH3:32])[C:3]=1[O:4][CH2:5][CH2:6][NH:7][C@@H:8]([CH3:18])[C@@H:9]([C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)[OH:10].Br[C:34]1[CH:42]=[CH:41][C:37]([C:38]([OH:40])=[O:39])=[CH:36][C:35]=1[CH3:43].[F-].[Cs+].O1CCOCC1>O1CCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.C(O)C>[OH:10][C@H:9]([C:11]1[CH:12]=[CH:13][C:14]([OH:17])=[CH:15][CH:16]=1)[C@@H:8]([NH:7][CH2:6][CH2:5][O:4][C:3]1[C:19]([CH3:32])=[CH:20][C:21]([C:34]2[CH:42]=[CH:41][C:37]([C:38]([OH:40])=[O:39])=[CH:36][C:35]=2[CH3:43])=[CH:22][C:2]=1[CH3:1])[CH3:18]

Komponenten

9

Edukt 4

HCID 25953Cesium fluorideHCID 312751,4-DioxaneHCID 821314-Bromo-3-methylbenzoic acidHCID 68544548HCID 68544548, Verbindung

Produkt 1

HCID 103890224'-{2-[(1S,2R)-2-Hydroxy-2-(4-hydroxyphenyl)-1-methylethylamino]ethoxy}-2,3',5'-trimethylbiphenyl-4-carboxylic acidAusbeute 22,6 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 702EthanolLösungsmittelHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of 4-((1R,2S)-2-{2-[2,6-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]ethylamino}-1-hydroxypropyl)phenol (0.02 g), 4-bromo-3-methylbenzoic acid (0.020 g), tetrakis(triphenylphosphine)palladium (0.0027 g), cesium fluoride (0.041 g), 1,4-dioxane (0.75 mL), ethanol (0.25 mL) and water (0.15 mL) was stirred at 100° C. overnight. After being cooled to room temperature, the reaction mixture was diluted with tetrahydrofuran (2.5 mL). The crude product was purified by SCX ion exchange column chromatography (Argonaut 1 g, preconditioning: tetrahydrofuran, washing solvent:tetrahydrofuran, eluent:2 mol/L ammonia in methanol), followed by reverse phase column chromatography (Shiseido Capcell Pak C18 ODS, 5 μm, 120 Å, 20×50 mm, linear gradient 0.1% aqueous formic acid/acetonitrile=90/10-60/40) to afford the title compound (0.0046 g) as a white amorphous. The structure and physical data were shown in table 1.

Aufarbeitung

  1. temperatureAfter being cooled to room temperature
  2. customThe crude product was purified by SCX ion exchange column chromatography (Argonaut 1 g, preconditioning: tetrahydrofuran, washing solvent:tetrahydrofuran, eluent:2 mol/L ammonia in methanol)

Quellen und Nachweise

ORD-Eintrag
ord-964b0ce4b8f2449da671bdc4fee56304
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07423185B2

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