Potassium Phosphate, Tribasic → [5-(4-{1-ethyl-1-[4-(3-ethyl-3-hydroxy-pentyl)-3-methyl-phenyl]-propyl}-phenyl)-pyridin-3-yl]-acetic Acid Methyl Ester

HRID 547074

Reaktionsgleichung

Reaktionsgleichung von HRID 547074
[CH3:1][O:2][C:3](=[O:12])[CH2:4][C:5]1[CH:6]=[N:7][CH:8]=[C:9](Br)[CH:10]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH2:50]([C:52]([OH:84])([CH2:82][CH3:83])[CH2:53][CH2:54][C:55]1[CH:60]=[CH:59][C:58]([C:61]([CH2:79][CH3:80])([C:64]2[CH:69]=[CH:68][C:67](B3OC(C)(C)C(C)(C)O3)=[CH:66][CH:65]=2)[CH2:62][CH3:63])=[CH:57][C:56]=1[CH3:81])[CH3:51].C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:1][O:2][C:3](=[O:12])[CH2:4][C:5]1[CH:6]=[N:7][CH:8]=[C:9]([C:67]2[CH:66]=[CH:65][C:64]([C:61]([CH2:79][CH3:80])([C:58]3[CH:59]=[CH:60][C:55]([CH2:54][CH2:53][C:52]([CH2:82][CH3:83])([OH:84])[CH2:50][CH3:51])=[C:56]([CH3:81])[CH:57]=3)[CH2:62][CH3:63])=[CH:69][CH:68]=2)[CH:10]=1

Komponenten

9

Edukt 5

HCID 62657Potassium Phosphate, TribasicHCID 516892Sodium BicarbonateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 23398394Methyl 2-(5-bromopyridin-3-yl)acetateHCID 577090723-Ethyl-1-(4-{1-ethyl-1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-pentan-3-ol

Produkt 1

HCID 57443529[5-(4-{1-ethyl-1-[4-(3-ethyl-3-hydroxy-pentyl)-3-methyl-phenyl]-propyl}-phenyl)-pyridin-3-yl]-acetic Acid Methyl EsterAusbeute 77 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

(5-Bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 35.2 mg, 0.153 mmol), palladium acetate (2.2 mg, 0.010 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (8.2 mg, 0.020 mmol), potassium phosphate (65 mg, 0.306 mmol) and water (0.2 mL) were added to a solution of 3-ethyl-1-(4-{1-ethyl-1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-pentan-3-ol (Example 145-(1); 48.8 mg, 0.102 mmol) in toluene (2 mL). After replacement with nitrogen, the mixture was stirred at 100° C. for 1.5 hours. The reaction mixture was then poured into a saturated aqueous sodium bicarbonate solution, followed by extraction with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=1:1) to give the target compound as a colorless oil (39.3 mg, 77%).

Aufarbeitung

  1. extractionfollowed by extraction with dichloromethane
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=1:1)

Quellen und Nachweise

ORD-Eintrag
ord-5b6c6439dea04e40b1e8f3ee689c3582
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07935688B2

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