3,4-dihydro-2H-pyran → 2-(4-bromo-3-fluorophenoxy)tetrahydro-2H-pyran

HRID 84240

Reaction equation

HRID 84240 reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH+]1C=CC=CC=1.[Br:18][C:19]1[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][C:20]=1[F:26].[O:27]1[CH:32]=[CH:31][CH2:30][CH2:29][CH2:28]1.CCOC(C)=O>ClCCl.CCCCCCC>[Br:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH:28]2[CH2:29][CH2:30][CH2:31][CH2:32][O:27]2)=[CH:21][C:20]=1[F:26]

Participants

7

Reactant 4

HCID 80803,4-dihydro-2H-pyranHCID 8857Ethyl AcetateHCID 27791534-Bromo-3-fluorophenolHCID 22033616Pyridinium.p-toluenesulfonate

Product 1

HCID 587212402-(4-bromo-3-fluorophenoxy)tetrahydro-2H-pyranYield 33%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8900HeptaneSolvent

Procedure

Pyridinium p-toluene sulfonic acid (789 mg, 3.1 mmol) was added to a solution of 4-bromo-3-fluorophenol (4.00 g, 20.9 mmol) and 3,4-dihydro-2H-pyran (3.52 g, 41.9 mmol) in dichloromethane (105 mL, 0.2M). After 2h the reaction was quenched with saturated aqueous sodium bicarbonate and the layers were separated. The aqueous layer was extracted with dichloromethane (2×). The organic layers were combined, dried (Na2SO4), filtered and concentrated to give a colorless oil. The material was loaded onto a 25g silica guard column and run on a 330g column with 0-5% EtOAc in heptane. Desired material was concentrated down yielding 1900 mg (33%) of a clear colorless oil.

Workup

  1. customAfter 2h the reaction was quenched with saturated aqueous sodium bicarbonate
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with dichloromethane (2×)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a colorless oil
  8. concentrationDesired material was concentrated

Sources & evidence

ORD record
ord-83d120aea195445e9ecc505c8ba48087
Source dataset
uspto-grants-2014_09
Patent number
US08846933B2

Linked notes

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