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

HRID 1183948Notes

Reaction equation

HRID 1183948 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 2 h 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 25 g silica guard column and run on a 330 g column with 0-5% EtOAc in heptane. Desired material was concentrated down yielding 1900 mg (33%) of a clear colorless oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.56-1.77 (m, 3H) 1.82-1.89 (m, 2H) 1.89-2.07 (m, 1H) 3.62 (m, J=11.37, 4.07, 4.07, 1.37 Hz, 1H) 3.85 (ddd, J=11.32, 10.05, 3.02 Hz, 1H) 5.38 (dd, J=3.12 Hz, 1H) 6.76 (ddd, J=8.88, 2.73, 1.07 Hz, 1H) 6.89 (dd, J=10.34, 2.73 Hz, 1H) 7.35-7.46 (m, 1H).

Workup

  1. customAfter 2 h 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-b6c7f8685eab4ac48f796723aacf3120
Source dataset
uspto-grants-2014_03
Patent number
US08664401B2

Reaction notes

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