Potassium Carbonate → 4-[(4-Bromophenyl)(tetrahydro-4H-pyran-4-ylidene)methyl]phenol

HRID 2100056Notes

Reaction equation

HRID 2100056 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)=O)=[CH:4][CH:3]=1.[O:17]1[CH2:22][CH2:21][C:20](=O)[CH2:19][CH2:18]1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.[Zn].Cl[Ti](Cl)(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[C:20]2[CH2:21][CH2:22][O:17][CH2:18][CH2:19]2)[C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 121599Tetrahydro-4H-pyran-4-oneHCID 4570728(4-Bromophenyl)(4-hydroxyphenyl)methanone

Product 1

HCID 686541974-[(4-Bromophenyl)(tetrahydro-4H-pyran-4-ylidene)methyl]phenolYield 62%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 24193Titanium TetrachlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

Zinc powder (0.759 g, 11.6 mmole) was suspended in THF (13 mL). TiCl4 (0.640 mL, 5.84 mmole) was added dropwise and the resulting mixture was heated to reflux for 60 min. A solution of (4-bromophenyl)(4-hydroxyphenyl)methanone (2) (0.404 g, 1.46 mmole) and tetrahydropyran-4-one (0.405 mL, 4.38 mmole) in THF (2 mL) was added. The resulting mixture was heated to reflux for 2 h, then was allowed to cool to RT. A 10% aqueous solution of K2CO3 (25 mL) was added and the mixture was filtered through a pad of Celite. The filtrate was separated and the aqueous layer was extracted with EtOAc (2×20 mL). The organics were washed with water (25 mL) and brine (25 mL), then dried (MgSO4) and concentrated. The residue was purified by silica gel chromatography (Isco Sg100c, RediSep 12 g cartridge and a gradient consisting of 10% EtOAc:hexanes for 5 min, 10% to 30% EtOAc:hexanes over 15 min, then 30% EtOAc:hexanes for 5 min) to provide 0.31 g (62%) of compound 46 as a white solid. 1H NMR (CDCl3): δ 7.41 (d, J=8.3 Hz, 2H), 6.97 (d, J=8.6 Hz, 2H), 6.95 (d, J=8.6 Hz, 2H), 6.75 (d, J=8.3 Hz, 2H), 4.97 (s, 1H), 3.72 (dd, J=10.0, 5.0 Hz, 4H), 2.40 (t, J=5.0 Hz, 2H), 2.36 (t, J=5.0 Hz, 2H).

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureto reflux for 60 min
  3. temperatureThe resulting mixture was heated
  4. temperatureto reflux for 2 h
  5. filtrationthe mixture was filtered through a pad of Celite
  6. customThe filtrate was separated
  7. extractionthe aqueous layer was extracted with EtOAc (2×20 mL)
  8. washThe organics were washed with water (25 mL) and brine (25 mL)
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated
  11. customThe residue was purified by silica gel chromatography (Isco Sg100c, RediSep 12 g cartridge
  12. wait10% to 30% EtOAc:hexanes over 15 min

Sources & evidence

ORD record
ord-efd779221b694f06a1ba639894b8ea3d
Source dataset
uspto-grants-2009_08
Patent number
US07569601B2

Reaction notes

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