Cesium fluoride → [6-Methoxy-2-(2,4,6-trifluoro-phenyl)-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone

HRID 1513925Notes

Reaction equation

HRID 1513925 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.[F-].[Cs+].B1(B2OCC(C)(C)CO2)OCC(C)(C)CO1.Br[C:57]1[C:62]([F:63])=[CH:61][C:60]([F:64])=[CH:59][C:58]=1[F:65]>C(#N)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([C:13]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]3)=[CH:16][CH:15]=1)=[O:29])=[C:8]([C:61]1[C:62]([F:63])=[CH:57][C:58]([F:65])=[CH:59][C:60]=1[F:64])[CH:7]=[CH:6]2

Participants

6

Reactant 4

HCID 25953Cesium fluorideHCID 753981-Bromo-2,4,6-trifluorobenzene2×HCID 2734316Bis(neopentyl glycolato)diboronHCID 11685250Trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)benzoyl]-naphthalen-2-yl ester

Product 1

HCID 57552534[6-Methoxy-2-(2,4,6-trifluoro-phenyl)-naphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanoneYield 69.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

Alternatively, combine trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (1.93 g, 3.60 mmol), cesium fluoride (5.0 g, 33 mmol), bis(neopentyl glycolato)diboron (1.0 g, 4.4 mmol), bis(tricyclohexylphosphine)palladium (0.50 g, 0.75 mmol) and acetonitrile (50 mL). Heat the mixture to 90° C. for 20 minutes to obtain a dark-colored solution. Add 2-bromo-1,3,5-trifluoro-benzene (5 g, 23.7 mmol) and heat at 90° C. for 2 hours. Add bis(tricyclohexylphosphine)palladium (0.50 g, 0.75 mmol) and 2-bromo-1,3,5-trifluoro-benzene (5.0 g, 23 mmol) and heat at 90° C. for 4 hours. Cool to room temperature and filter through a pad of celite and evaporate the solvent. Purify the residue over silica gel, eluting the material with methanol in dichloromethane (0 to 5%), to give 1.30 g (67%) of title compound: mass spectrum (ion spray) m/z=520.2 (M+H).

Workup

  1. customto obtain a dark-colored solution
  2. temperatureCool to room temperature
  3. filtrationfilter through a pad of celite
  4. customevaporate the solvent
  5. customPurify the residue over silica gel
  6. washeluting the material with methanol in dichloromethane (0 to 5%)

Sources & evidence

ORD record
ord-51b8c92683c446678622e36e209a1189
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

Loading…