Acetone → [4-(5-Acetyl-6-hydroxy-biphenyl-2-yloxymethyl)-phenyl]-(hydroxy-methyl]-benzonitrile

HRID 1161092Notes

Reaction equation

HRID 1161092 reaction equation
[OH:1][C:2]1[C:7]([C:8](=[O:10])[CH3:9])=[CH:6][CH:5]=[C:4]([OH:11])[C:3]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.IC[C:20]1[CH:25]=C[C:23]([CH:26](OC2CCCCO2)[C:27]2[CH:28]=[C:29]([CH:32]=[CH:33][CH:34]=2)[C:30]#[N:31])=[CH:22][CH:21]=1.[C:42](=[O:45])([O-])[O-].[K+].[K+].[Cl-].[NH4+].[CH3:50]C(C)=O>>[C:8]([C:7]1[CH:6]=[CH:5][C:4]([O:11][CH2:50][C:21]2[CH:20]=[CH:25][C:26]([C:27]3[C:28]([CH2:42][OH:45])=[C:29]([CH:32]=[CH:33][CH:34]=3)[C:30]#[N:31])=[CH:23][CH:22]=2)=[C:3]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:2]=1[OH:1])(=[O:10])[CH3:9]

Participants

6

Reactant 5

HCID 180AcetoneHCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 573554611-(2,6-Dihydroxy[1,1'-biphenyl]-3-yl)ethan-1-oneHCID 57438306HCID 57438306, compound

Product 1

HCID 86620598[4-(5-Acetyl-6-hydroxy-biphenyl-2-yloxymethyl)-phenyl]-(hydroxy-methyl]-benzonitrile

Conditions

Temperature
50 °C

Procedure

To a solution of 1-(2,6-dihydroxy-biphenyl-3-yl)-ethanone (446 mg, 1.95 mmol) and 3-[(4-iodomethyl-phenyl)-(tetrahydro-pyran-2-yloxy)-methyl]-benzonitrile (848 mg, 1.95 mmol) in acetone (50 mL) is added potassium carbonate (450 mg, 3.25 mmol). The suspension is heated at 50° C. for 14 hours. After cooling to room temperature, the mixture is poured onto saturated ammonium chloride (15 mL) and extracted with ethyl acetate (4×20 mL). The combined organic extracts are combined; washed with brine; dried over magnesium sulfate; filtered and concentrated under reduced pressure to a light-yellow oil: MS (m/z): 523 (M+). The residue is then dissolved in methanol and p-toluenesulfonic acid monohydrate is added. After 1 hour, the solvent is removed under reduced pressure. The resulting residue is purified by flash chromatography (20% to 45% ethyl acetate/hexanes) to give the title compound as a foam: MS (m/z): 449 (M+), 432 (M−OH).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with ethyl acetate (4×20 mL)
  3. washwashed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure to a light-yellow oil
  7. dissolutionThe residue is then dissolved in methanol
  8. additionp-toluenesulfonic acid monohydrate is added
  9. customthe solvent is removed under reduced pressure
  10. customThe resulting residue is purified by flash chromatography (20% to 45% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-8412faed80d54c949619c865663b2164
Source dataset
uspto-grants-2010_10
Patent number
US07816523B2

Reaction notes

Loading…