Triphenylphosphine → 3-(4-[2-(2-Cyclohexyl-5-methyl-oxazol-4-yl)-ethoxy]-phenyl}-2-methyl-2-(3-thiophen-3-yl-phenoxy)-propionic acid ethyl ester

HRID 585290Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 585290
BrC1C=C(C=CC=1)OC(C)(CC1C=CC(OCCC2N=C(C3CCCCC3)OC=2C)=CC=1)C(O)=O.[S:36]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F-].[K+].[CH2:65]([O:67][C:68](=[O:100])[C:69]([CH3:99])([O:92][C:93]1[CH:98]=[CH:97][CH:96]=[CH:95][CH:94]=1)[CH2:70][C:71]1[CH:76]=[CH:75][C:74]([O:77][CH2:78][CH2:79][C:80]2[N:81]=[C:82]([CH:86]3[CH2:91][CH2:90][CH2:89][CH2:88][CH2:87]3)[O:83][C:84]=2[CH3:85])=[CH:73][CH:72]=1)[CH3:66]>C1COCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C>[CH2:65]([O:67][C:68](=[O:100])[C:69]([CH3:99])([O:92][C:93]1[CH:94]=[CH:95][CH:96]=[C:97]([C:38]2[CH:39]=[CH:40][S:36][CH:37]=2)[CH:98]=1)[CH2:70][C:71]1[CH:72]=[CH:73][C:74]([O:77][CH2:78][CH2:79][C:80]2[N:81]=[C:82]([CH:86]3[CH2:91][CH2:90][CH2:89][CH2:88][CH2:87]3)[O:83][C:84]=2[CH3:85])=[CH:75][CH:76]=1)[CH3:66]

Komponenten

9

Edukt 5

HCID 11776TriphenylphosphineHCID 522689Potassium FluorideHCID 581760Thiophene-3-boronic acidHCID 208231432-Methyl-3-(4-{2-[5-methyl-2-cyclohexyl-oxazol-4-yl]-ethoxy}-phenyl)-2-phenoxypropionic Acid Ethyl EsterHCID 223400282-(3-Bromo-phenoxy)-3-(4-[2-(2-cyclohexyl-5-methyl-oxazol-4-yl)-ethoxy]-phenyl}-2-methyl-propionic acid

Produkt 1

HCID 208231423-(4-[2-(2-Cyclohexyl-5-methyl-oxazol-4-yl)-ethoxy]-phenyl}-2-methyl-2-(3-thiophen-3-yl-phenoxy)-propionic acid ethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Add palladium acetate (8 mg, 0.04 mmol) to a solution of 2-(3-Bromo-phenoxy)-3-(4-[2-(2-cyclohexyl-5-methyl-oxazol-4-yl)-ethoxy]-phenyl}-2-methyl-propionic acid (0.204 g, 0.36 mmol), thiophene-3-boronic acid (91 mg, 0.71 mmol), triphenylphosphine (19 mg, 0.07 mmol), and potassium fluoride (51 mg, 1.07 mmol) in anhydrous THF (3 mL). Reflux the reaction mixture for 18 h under an atmosphere of nitrogen. Dilute the cooled reaction mixture with ethyl acetate and wash with water and brine. The organic layer was dried over Na2SO4, concentrated in vacuo, and purified by flash column chromatography (9% acetone in hexanes) to provide a mixture of the titled compound and 3-{4-[2-(2-Cyclohexyl-5-methyl-oxazol-4-yl)-ethoxy]-phenyl}-2-methyl-2-phenoxy-propionic acid ethyl ester (70 mg, 34%). 1H NMR (400 MHz, CDCl3): δ 7.38-7.19 (m, 5H), 7.13 (d, 2H, J=8.60 Hz), 7.07 (m, 1H), 6.80 (2H, J=8.60 Hz), 6.73-6.70 (m, 1H), 4.19 (q, 2H, J=7.04 Hz), 4.12 (t, 2H, J=6.65 Hz), 3.27 (d, 1H, J=13.69 Hz), 3.11 (d, 1H, J=13.69 Hz), 2.85 (t, 2H, J=6.65 Hz), 2.70-2.63 (m, 1H), 2.22 (s, 3H), 2.01 (d, 2H, J=11.73 Hz), 1.79-1.76 (m, 2H), 1.67 (h, 1H, J=11.73 Hz), 1.59 (s, 3H), 1.56-1.46 (m, 2H), 1.41 (s, 3H), 1.37-1.23 (m, 2H), 1.20 (t, 3H, J=7.04 Hz). MS [EI+] 574 (M+H)+. Rf=0.08 in 9% ethyl acetate in hexanes.

Aufarbeitung

  1. temperatureReflux the reaction mixture for 18 h under an atmosphere of nitrogen
  2. additionDilute
  3. washwash with water and brine
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. custompurified by flash column chromatography (9% acetone in hexanes)
  7. customto provide

Quellen und Nachweise

ORD-Eintrag
ord-8f0e0cf817eb48c08a13b07610cb3faf
Quelldatensatz
uspto-grants-2005_08
Patentnummer
US06930120B2

Notizen zur Reaktion

Wird geladen…