Cesium fluoride → 1-(2-{4-[2-(3,5-Dimethyl-4-methylsulfonyl-phenyl)-6-methoxy-naphthalen-1-yloxy]-phenoxy}-ethyl)-piperidine

HRID 748967노트

반응식

HRID 748967 반응식
C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[F-].[Cs+].[CH2:22]([O:29][C:30]1[CH:31]=[CH:32][C:33]2[C:37]([O:38][C:39]3[CH:53]=[CH:52][C:42]([O:43][CH2:44][CH2:45][N:46]4[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]4)=[CH:41][CH:40]=3)=[C:36]([C:54]3[CH:59]=CC(S(C)(=O)=O)=C(F)C=3)S[C:34]=2[CH:65]=1)C1C=CC=CC=1.B1(B2OCC(C)(C)CO2)OCC(C)(C)CO1.Br[C:83]1[CH:84]=[C:85]([CH3:94])[C:86]([S:90]([CH3:93])(=[O:92])=[O:91])=[C:87]([CH3:89])[CH:88]=1>C(#N)C.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:94][C:85]1[CH:84]=[C:83]([C:36]2[CH:54]=[CH:59][C:34]3[C:33](=[CH:32][CH:31]=[C:30]([O:29][CH3:22])[CH:65]=3)[C:37]=2[O:38][C:39]2[CH:40]=[CH:41][C:42]([O:43][CH2:44][CH2:45][N:46]3[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]3)=[CH:52][CH:53]=2)[CH:88]=[C:87]([CH3:89])[C:86]=1[S:90]([CH3:93])(=[O:92])=[O:91]

참가 물질

9

반응물 5

HCID 25953Cesium fluorideHCID 75806TricyclohexylphosphineHCID 2734316Bis(neopentyl glycolato)diboronHCID 59751449(2-{4-[6-Benzyloxy-2-(3-fluoro-4-methanesulfonyl-phenyl)-benzo[b]thiophen-3-yloxy]-phenoxy}-ethyl)-piperidineHCID 685159425-Bromo-2-methanesulfonyl-1,3-dimethyl-benzene

생성물 1

HCID 597514541-(2-{4-[2-(3,5-Dimethyl-4-methylsulfonyl-phenyl)-6-methoxy-naphthalen-1-yloxy]-phenoxy}-ethyl)-piperidine수율 84.6%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 6342Acetonitrile용매2회HCID 8857Ethyl Acetate용매

반응 조건

온도
90 °C

실험 절차

Combine palladium (II) acetate (13 mg, 0.06 mmol), tricyclohexylphosphine (27 mg, 0.10 mmol), cesium fluoride (518 mg, 3.4 mmol) and acetonitrile (10 mL). Stir for 5 minutes. Add the compound of Preparation 1 (200 mg, 0.38 mmol) and bis(neopentylglycolato)diboron (129 mg, 0.57 mmol). Heat to 90° C. for 1 minute and add 5-bromo-2-methanesulfonyl-1,3-dimethyl-benzene (110 mg, 0.42 mmol) in acetonitrile (4 mL). Stir at 90° C. for 10 minutes. Cool to room temperature and dilute the solution with ethyl acetate (20 mL) and wash with saturated aqueous NaHCO3 (10 mL). Separate the layers, wash the organic layer with brine, dry with MgSO4, filter, and concentrate in vacuo. Chromatograph the residue on a SiO2 column eluting with methanol (4%) in dichloromethane to give 180 mg (76%) of the title compound. Mass spectrum (ion spray): m/z=560.3 (M+H).

후처리

  1. additionAdd
  2. stirringStir at 90° C. for 10 minutes
  3. temperatureCool to room temperature
  4. washwash with saturated aqueous NaHCO3 (10 mL)
  5. customSeparate the layers
  6. washwash the organic layer with brine
  7. dry with materialdry with MgSO4
  8. filtrationfilter
  9. concentrationconcentrate in vacuo
  10. washChromatograph the residue on a SiO2 column eluting with methanol (4%) in dichloromethane

출처 및 근거

ORD 기록
ord-cff54c2a8af9425e8388dc31b2d76daf
출처 데이터셋
uspto-grants-2008_07
특허 번호
US07399867B2

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