Cesium fluoride → 1-(2-{4-[2-(4-Methanesulfonyl-3-methylsulfanyl-phenyl)-6-methoxy-naphthalen-1-yloxy]-phenoxy}-ethyl)-piperidine

HRID 748969Notes

Reaction equation

HRID 748969 reaction equation
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]3C=CC(S(C)(=O)=O)=C(F)[CH:55]=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:88]=[CH:87][C:86]([S:89]([CH3:92])(=[O:91])=[O:90])=[C:85]([S:93][CH3:94])[CH:84]=1>C(#N)C.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:92][S:89]([C:86]1[CH:87]=[CH:88][C:83]([C:36]2[CH:54]=[CH:55][C:32]3[C:33](=[CH:34][CH:65]=[C:30]([O:29][CH3:22])[CH:31]=3)[C:37]=2[O:38][C:39]2[CH:53]=[CH:52][C:42]([O:43][CH2:44][CH2:45][N:46]3[CH2:47][CH2:48][CH2:49][CH2:50][CH2:51]3)=[CH:41][CH:40]=2)=[CH:84][C:85]=1[S:93][CH3:94])(=[O:91])=[O:90]

Participants

9

Reactant 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 685174084-Bromo-1-(methanesulfonyl)-2-(methylsulfanyl)benzene

Product 1

HCID 597514241-(2-{4-[2-(4-Methanesulfonyl-3-methylsulfanyl-phenyl)-6-methoxy-naphthalen-1-yloxy]-phenoxy}-ethyl)-piperidineYield 68.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

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 4-bromo-1-methanesulfonyl-2-methylsulfanyl-benzene (118 mg, 0.42 mmol) in acetonitrile (4 mL). Stir at 90° C. for 10 minutes. Cool to room temperature and dilute the solution with EtOAc (20 mL) and wash with saturated aqueous NaHCO3 (10 mL). Separate the layers, wash the organic layer with brine (10 mL), dry with MgSO4, filter, and concentrate in vacuo. Chromatograph the residue on a SiO2 column eluting with methanol (4%) in dichloromethane to give 150 mg (64%) of the title compound. Mass spectrum (ion spray): m/z=578.3 (M+H).

Workup

  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 (10 mL)
  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

Sources & evidence

ORD record
ord-de88f0deb6d94a148722c3f25f4acf8e
Source dataset
uspto-grants-2008_07
Patent number
US07399867B2

Reaction notes

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