Cesium fluoride → Acetic acid 6-(4-methanesulfonyl-3-methoxy-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalen-2-yl ester

HRID 732812Notes

Reaction equation

HRID 732812 reaction equation
C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[F-].[Cs+].[N:22]1([CH2:28][CH2:29][O:30][C:31]2[CH:59]=[CH:58][C:34]([O:35][C:36]3[C:45](OS(C(F)(F)F)(=O)=O)=[CH:44][CH:43]=[C:42]4[C:37]=3[CH:38]=[CH:39][C:40]([O:54][C:55](=[O:57])[CH3:56])=[CH:41]4)=[CH:33][CH:32]=2)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1.[CH3:60][S:61]([C:64]1[CH:69]=[CH:68][C:67](OS(C(F)(F)F)(=O)=O)=[CH:66][C:65]=1[O:78][CH3:79])(=[O:63])=[O:62]>CC#N.CC([O-])=O.CC([O-])=O.[Pd+2].O>[CH3:60][S:61]([C:64]1[CH:69]=[CH:68][C:67]([C:45]2[C:36]([O:35][C:34]3[CH:58]=[CH:59][C:31]([O:30][CH2:29][CH2:28][N:22]4[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]4)=[CH:32][CH:33]=3)=[C:37]3[C:42](=[CH:43][CH:44]=2)[CH:41]=[C:40]([O:54][C:55](=[O:57])[CH3:56])[CH:39]=[CH:38]3)=[CH:66][C:65]=1[O:78][CH3:79])(=[O:63])=[O:62]

Participants

8

Reactant 4

HCID 25953Cesium fluorideHCID 75806TricyclohexylphosphineHCID 583385445-(4-(2-(Piperidin-1-yl)ethoxy)phenoxy)-6-(trifluoromethylsulfonyloxy)naphthalen-2-yl acetateHCID 86607165Trifluoro-methanesulfonic acid 4-methanesulfonyl-3-methoxy-phenyl ester

Product 1

HCID 59751425Acetic acid 6-(4-methanesulfonyl-3-methoxy-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-naphthalen-2-yl esterYield 33%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

Combine Pd(OAc)2 (46 mg, 0.20 mmol), tricyclohexylphosphine (95 mg, 0.34 mmol), and CsF (1.85 g, 12.26 mmol) in CH3CN (20 mL) under N2. Stir the reaction mixture for 5 minutes. Add acetic acid 5-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-6-trifluoromethanesulfonyloxy-naphthalen-2-yl ester (730 mg, 1.36 mmol) and bis(neopentyl glycolate)diboron (460 mg, 2.04 mmol) to the reaction mixture. Heat to 90° C. and stir for about 5 minutes. Add trifluoro-methanesulfonic acid 4-methanesulfonyl-3-methoxy-phenyl ester (500 mg, 1.5 mmol) and continue to heat the mixture for two hours. Cool to room temperature, add water (100 mL), and extract the aqueous layer with CH2Cl2 (3×100 mL). Combine the organic layers and dry with Na2SO4, filter and concentrate. Purify by flash column chromatography (silica gel, 0 to 5% MeOH/CH2Cl2) to give 260 mg of the title compound (33%): mass spectrum (ion spray): m/z=590.4 (M+H).

Workup

  1. stirringstir for about 5 minutes
  2. temperatureto heat the mixture for two hours
  3. temperatureCool to room temperature
  4. extractionextract the aqueous layer with CH2Cl2 (3×100 mL)
  5. dry with materialCombine the organic layers and dry with Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate
  8. customPurify by flash column chromatography (silica gel, 0 to 5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-0fa3cb1afd364d2f988de126ef566351
Source dataset
uspto-grants-2009_09
Patent number
US07585977B2

Reaction notes

Loading…