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 585290노트

반응식

HRID 585290 반응식
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]

참가 물질

9

반응물 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

생성물 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

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-8f0e0cf817eb48c08a13b07610cb3faf
출처 데이터셋
uspto-grants-2005_08
특허 번호
US06930120B2

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