Cesium fluoride → 1-[2-[4-[[6-Methoxy-2-(5-methylsulfonyl-3-thienyl)-1-naphthyl]oxy]phenoxy]ethyl]piperidine

HRID 445223Notes

Reaction equation

HRID 445223 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([O:13][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.C[Sn](C)(C)[C:39]1[CH:43]=[C:42]([S:44]([CH3:47])(=[O:46])=[O:45])[S:41][CH:40]=1.[F-].[Cs+]>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([O:13][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]([C:39]1[CH:43]=[C:42]([S:44]([CH3:47])(=[O:46])=[O:45])[S:41][CH:40]=1)[CH:7]=[CH:6]2

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 116133766-Methoxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)naphthalen-2-yl trifluoromethanesulfonateHCID 58338539Trimethyl-(5-methylsulfonyl-3-thienyl)stannane

Product 1

HCID 583385611-[2-[4-[[6-Methoxy-2-(5-methylsulfonyl-3-thienyl)-1-naphthyl]oxy]phenoxy]ethyl]piperidineYield 57.9%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
90 °C

Procedure

Combine palladium(II)acetate (0.043 g 0.19 mmol) and trycyclohexylphosphine (0.081 g, 0.29 mmol) in acetonitrile (15 mL) and sonicate for 10 minutes. Add [6-methoxy-1-[4-[2-(1-piperidyl)ethoxy]phenoxy]-2-naphthyl]trifluoromethanesulfonate (0.5 g, 0.95 mmol), trimethyl-(5-methylsulfonyl-3-thienyl)stannane (0.94 g, 2.9 mmol) and palladium mixture to a suspension of cesium fluoride (0.5 g, 3.3 mmol) in acetonitrile (40 mL). Warm the resulting mixture to 90° C. and stir for 18 hours. Cool the mixture to room temperature and concentrate. Partition the resulting residue between ethylacetate and saturated aqueous sodium bicarbonate. Separate the layers and wash the organic layer with saturated aqueous ammonium chloride and brine, then dry with sodium sulfate. Concentrate the resulting solution and purify by flash chromatography (0-5% methanol in dichloromethane) to obtain the title compound (0.3 g, 0.55 mmol).

Workup

  1. customsonicate for 10 minutes
  2. temperatureCool the mixture to room temperature
  3. concentrationconcentrate
  4. customPartition the resulting residue between ethylacetate and saturated aqueous sodium bicarbonate
  5. customSeparate the layers
  6. washwash the organic layer with saturated aqueous ammonium chloride and brine
  7. dry with materialdry with sodium sulfate
  8. concentrationConcentrate the resulting solution
  9. custompurify by flash chromatography (0-5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-0deb72a22e974dd38dda7abf22a2a45f
Source dataset
uspto-grants-2013_07
Patent number
US08476300B2

Reaction notes

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