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

HRID 748967ノート

反応式

HRID 748967 の反応式
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]

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 6342Acetonitrile溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
90 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-cff54c2a8af9425e8388dc31b2d76daf
出典データセット
uspto-grants-2008_07
特許番号
US07399867B2

反応ノート

読み込み中…