Trifluoromethanesulfonic acid → HCID 59526859, compound

HRID 384476Notes

Reaction equation

HRID 384476 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH2:8][OH:9])[CH:5]=[CH:4][N:3]=1.FC(F)(F)S(O)(=O)=O.[O:18]1[CH2:23][CH2:22][CH:21]([CH2:24]O)[CH2:20][CH2:19]1.C(=O)([O-])O.[Na+]>ClCCl.C(N(CC)CC)C>[F:1][C:2]1[CH:7]=[C:6]([CH2:8][O:9][CH2:24][CH:21]2[CH2:22][CH2:23][O:18][CH2:19][CH2:20]2)[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 62406Trifluoromethanesulfonic acidHCID 516892Sodium BicarbonateHCID 2773573(Oxan-4-yl)methanolHCID 11332468(2-Fluoropyridin-4-yl)methanol

Product 1

HCID 59526859HCID 59526859, compoundYield 24.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a mixture of (2-fluoropyridin-4-yl)methanol (300 mg), triethylamine (239 mg), and dichloromethane (24 mL) was added anhydrous trifluoromethanesulfonic acid (666 mg) under ice-cooling, followed by stirring at the same temperature for 1 hour. (Tetrahydro-2H-pyran-4-yl)methanol (1.37 g) was added to the reaction liquid at room temperature, followed by stirring at the same temperature for 8 hours. A saturated aqueous sodium hydrogen carbonate solution (20 mL) was added to the reaction mixture, followed by extraction with chloroform (30 mL). The organic layer was washed with saturated brine and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and then the residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=8/1) to obtain 2-fluoro-4-[(tetrahydro-2H-pyran-4-ylmethoxy)methyl]pyridine (132 mg).

Workup

  1. temperaturecooling
  2. stirringby stirring at the same temperature for 8 hours
  3. extractionfollowed by extraction with chloroform (30 mL)
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=8/1)

Sources & evidence

ORD record
ord-b753b3f4c2084e89a413e281c1386a96
Source dataset
uspto-grants-2013_02
Patent number
US08367702B2

Reaction notes

Loading…