Tetrahydro-4H-pyran-4-one → 4-(3,5-Difluorophenyl)oxan-4-ol

HRID 705196Notes

Reaction equation

HRID 705196 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([F:9])[CH:3]=1.[O:10]1[CH2:15][CH2:14][C:13](=[O:16])[CH2:12][CH2:11]1>C1COCC1>[F:9][C:4]1[CH:3]=[C:2]([C:13]2([OH:16])[CH2:14][CH2:15][O:10][CH2:11][CH2:12]2)[CH:7]=[C:6]([F:8])[CH:5]=1

Participants

4

Reactant 2

HCID 121599Tetrahydro-4H-pyran-4-oneHCID 1363131-Bromo-3,5-difluorobenzene

Product 1

HCID 193886354-(3,5-Difluorophenyl)oxan-4-olYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 1-bromo-3,5-difluorobenzene (1.6 equiv.) in THF (0.26 M) under Ar was added Mg turnings (1.6 equiv.). A reflux condenser was attached and the solution was submerged in a 90° C. oil bath and refluxed for two hours. The dihydro-2H-pyran-4(3H)-one (1.0 equiv.) was added in THF via syringe. The solution was left stirring at rt under Ar for 5 hrs. The reaction solution was quenched by addition of NH4Cl(sat) and the solution was extracted with EtOAc, washed with NaCl(sat), dried over MgSO4, filtered, concentrated and purified by ISCO SiO2 chromatography (0-100% EtOAc/n-heptanes gradient) to yield 4-(3,5-difluorophenyl)tetrahydro-2H-pyran-4-ol in 71% yield. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.59-1.68 (m, 3 H), 2.07-2.19 (m, 2 H), 3.87-3.93 (m, 4 H), 6.72 (tt, J=8.75, 2.20 Hz, 1 H), 6.97-7.06 (m, 2 H).

Workup

  1. customA reflux condenser was attached
  2. customwas submerged in a 90° C.
  3. temperaturerefluxed for two hours
  4. waitThe solution was left
  5. customThe reaction solution was quenched by addition of NH4Cl(sat)
  6. extractionthe solution was extracted with EtOAc
  7. washwashed with NaCl(sat)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. custompurified by ISCO SiO2 chromatography (0-100% EtOAc/n-heptanes gradient)

Sources & evidence

ORD record
ord-82da2eda0839446186a761efd85b979b
Source dataset
uspto-grants-2015_11
Patent number
US09173883B2

Reaction notes

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