Cesium fluoride → Methanesulfonic acid 6-(4-fluoro-2-methylsulfanyl-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester

HRID 1513941Notes

Reaction equation

HRID 1513941 reaction equation
[CH3:1][S:2]([O:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[C:12]([C:16](=[O:32])[C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][N:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)=[CH:19][CH:18]=1)=[C:11](OS(C(F)(F)F)(=O)=O)[CH:10]=[CH:9]2)(=[O:4])=[O:3].[CH3:41][S:42][C:43]1[CH:48]=[C:47]([F:49])[CH:46]=[CH:45][C:44]=1B(O)O.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[F-].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:49][C:47]1[CH:46]=[CH:45][C:44]([C:11]2[C:12]([C:16](=[O:32])[C:17]3[CH:18]=[CH:19][C:20]([O:23][CH2:24][CH2:25][N:26]4[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]4)=[CH:21][CH:22]=3)=[C:13]3[C:8](=[CH:9][CH:10]=2)[CH:7]=[C:6]([O:5][S:2]([CH3:1])(=[O:3])=[O:4])[CH:15]=[CH:14]3)=[C:43]([S:42][CH3:41])[CH:48]=1

Participants

6

Reactant 4

HCID 25953Cesium fluorideHCID 75806TricyclohexylphosphineHCID 11628623Trifluoromethanesulfonic acid 6-methanesulfonyloxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl esterHCID 532165234-Fluoro-2-(methylthio)phenylboronic acid

Product 1

HCID 11238709Methanesulfonic acid 6-(4-fluoro-2-methylsulfanyl-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl esterYield 92%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

Charge a flask with trifluoromethanesulfonic acid 6-methanesulfonyloxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (10.0 g, 16.6 mmol), 2-methylsulfanyl-4-fluoro-benzene boronic acid (7.7 g, 41.6 mmol), palladium acetate (371 mg, 1.66 mmol, tricyclohexylphosphine (700 mg, 2.5 mmol) and cesium fluoride (13 g, 83 mmol) and purge with nitrogen. Dilute with degassed acetonitrile (150 mL) and plunge into an 80° C. oil bath. Cool to room temperature after 1.5 hours and filter through celite and concentrate in vacuo. Partition the residue between methylene chloride and saturate aqueous sodium bicarbonate. Dry the organic layer with sodium sulfate, filter and concentrate. Purify the residue over a silica gel column, eluting with 2% methanol in methylene chloride, to yield 9.0 g (92%) of the title compound. LCMS Rt (0.01% heptafluorobutyric acid:1.0% isopropylalcohol:water is mobile phase A and 0.01% heptafluorobutyric acid:1.0% isopropylalcohol:acetonitrile is mobile phase B; gradient method 25 to 95% B, Purity@254 nm)=2.92 min (95%); mass spectrum (ion spray): m/z=594.3 (M+H).

Workup

  1. custompurge with nitrogen
  2. additionDilute with degassed acetonitrile (150 mL) and plunge into an 80° C. oil bath
  3. filtrationfilter through celite
  4. concentrationconcentrate in vacuo
  5. customPartition the residue between methylene chloride
  6. concentrationsaturate aqueous sodium bicarbonate
  7. dry with materialDry the organic layer with sodium sulfate
  8. filtrationfilter
  9. concentrationconcentrate
  10. customPurify the residue over a silica gel column
  11. washeluting with 2% methanol in methylene chloride

Sources & evidence

ORD record
ord-2838533b43244e9fbd2983c9606664ce
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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