Cesium fluoride → [2-(2,5-Difluoro-phenyl)-6-methoxy-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone

HRID 1513881Notes

Reaction equation

HRID 1513881 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([C:13](=[O:29])[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:16][CH:15]=1)=[C:8](OS(C(F)(F)F)(=O)=O)[CH:7]=[CH:6]2.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[F-].[Cs+].[F:59][C:60]1[CH:65]=[CH:64][C:63]([F:66])=[CH:62][C:61]=1B(O)O>C(#N)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:59][C:60]1[CH:65]=[CH:64][C:63]([F:66])=[CH:62][C:61]=1[C:8]1[CH:7]=[CH:6][C:5]2[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=2)[C:9]=1[C:13]([C:14]1[CH:15]=[CH:16][C:17]([O:20][CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)=[CH:18][CH:19]=1)=[O:29]

Participants

7

Reactant 4

HCID 25953Cesium fluorideHCID 75806TricyclohexylphosphineHCID 2734335(2,5-Difluorophenyl)boronic acidHCID 11685250Trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)benzoyl]-naphthalen-2-yl ester

Product 1

HCID 57552548[2-(2,5-Difluoro-phenyl)-6-methoxy-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanoneYield 68%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

Dissolve trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (4.51 g, 8.4 mmol) in acetonitrile (140 mL). Add Pd(OAc)2 (0.28 g, 1.3 mmol), tricyclohexylphosphine (0.59 g, 2.1 mmol), cesium fluoride (11.4 g, 75.6 mmol) and 2,5-difluorobenzeneboronic acid (2.56 g, 16.2 mmol). Flush the flask with nitrogen then heat the reaction mixture to 90° C. Heat the reaction mixture for one hour and then cool it to room temperature. Add water (400 mL) and extract the aqueous layer with methylene chloride (3×400 mL). Combine the organic layers and dry with sodium sulfate, filter, concentrate and purify by flash column chromatography (0-4% MeOH—NOH (10/1, v/v)/CH2Cl2) to give 2.42 g (68%) of the title compound: mass spectrum (ion spray) m/z=502.3 (M+H).

Workup

  1. customFlush the flask with nitrogen
  2. temperatureHeat the reaction mixture for one hour
  3. temperaturecool it to room temperature
  4. extractionAdd water (400 mL) and extract the aqueous layer with methylene chloride (3×400 mL)
  5. dry with materialCombine the organic layers and dry with sodium sulfate
  6. filtrationfilter
  7. concentrationconcentrate
  8. custompurify by flash column chromatography (0-4% MeOH—NOH (10/1

Sources & evidence

ORD record
ord-be5e90d18c3e4ffc87ef2e0d01cb5f96
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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