Potassium Carbonate → HCID 68309916, compound

HRID 1021317Notes

Reaction equation

HRID 1021317 reaction equation
[Si]([O:8][CH2:9][C:10]1[C:11]([F:26])=[C:12]([N:16]2[CH2:19][CH:18]([CH2:20]CS([O-])(=O)=O)[CH2:17]2)[CH:13]=[CH:14][CH:15]=1)(C(C)(C)C)(C)C.[CH3:27][C:28]1[N:33]=[CH:32][C:31]([OH:34])=[CH:30][CH:29]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[F:26][C:11]1[C:12]([N:16]2[CH2:17][CH:18]([CH2:20][O:34][C:31]3[CH:32]=[N:33][C:28]([CH3:27])=[CH:29][CH:30]=3)[CH2:19]2)=[CH:13][CH:14]=[CH:15][C:10]=1[CH2:9][OH:8]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 142752-Methyl-5-hydroxypyridineHCID 86686253HCID 86686253, compound

Product 1

HCID 68309916HCID 68309916, compoundYield 65.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

{1-[3-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]azetidin-3-yl}methylmethanesulfonate (150 mg), 6-methylpyridin-3-ol (70 mg), and DMF (2 ml) were mixed, and potassium carbonate (120 mg) were added thereto, followed by stirring at 80° C. for 6 hours. The reaction mixture was concentrated under reduced pressure, and CHCl3 and a saturated aqueous sodium hydrogen carbonate solution were then added thereto. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. THF (2 ml) and a 1 M TBAF/THF solution (0.6 ml) were added to the obtained residue, followed by stirring at room temperature for 1 hour. CHCl3 and a saturated aqueous ammonium chloride solution were added to the reaction mixture, and the organic layer was dried over Na2SO4 and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/EtOAc) to obtain [2-fluoro-3-(3-{[(6-methylpyridin-3-yl)oxy]methyl}azetidin-1-yl)phenyl]methanol (74 mg).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, and CHCl3
  2. additiona saturated aqueous sodium hydrogen carbonate solution were then added
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. additionTHF (2 ml) and a 1 M TBAF/THF solution (0.6 ml) were added to the obtained residue
  6. stirringby stirring at room temperature for 1 hour
  7. additionCHCl3 and a saturated aqueous ammonium chloride solution were added to the reaction mixture
  8. dry with materialthe organic layer was dried over Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. customThe obtained residue was purified by silica gel column chromatography (hexane/EtOAc)

Sources & evidence

ORD record
ord-f2922e4129394464be416a6c80993cc2
Source dataset
uspto-grants-2014_05
Patent number
US08716470B2

Reaction notes

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