1-(2,3-Dihydro-1-benzofuran-5-yl)propan-1-one → 4-(1-(4-(2-Chloroethoxy)phenyl)-2-(2,3-dihydrobenzofuran-5-yl) but-1-enyl)phenol

HRID 626207Notes

Reaction equation

HRID 626207 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10](=O)[CH2:11][CH3:12])=[CH:9][C:4]=2[CH2:3][CH2:2]1.[Cl:14][CH2:15][CH2:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([C:26]2[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=2)=O)=[CH:20][CH:19]=1>C1COCC1.[Zn].Cl[Ti](Cl)(Cl)Cl>[Cl:14][CH2:15][CH2:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([C:26]2[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=2)=[C:10]([C:8]2[CH:7]=[CH:6][C:5]3[O:1][CH2:2][CH2:3][C:4]=3[CH:9]=2)[CH2:11][CH3:12])=[CH:20][CH:19]=1

Participants

6

Reactant 2

HCID 40673881-(2,3-Dihydro-1-benzofuran-5-yl)propan-1-oneHCID 89656364[4-(2-Chloroethoxy)phenyl](4-hydroxyphenyl)methanone

Product 1

HCID 896574494-(1-(4-(2-Chloroethoxy)phenyl)-2-(2,3-dihydrobenzofuran-5-yl) but-1-enyl)phenolYield 78.3%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 24193Titanium TetrachlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of Zn (595 mg, 6 eq) in 20 mL anhydrous THF was added TiCl4 (0.5 mL, 3 eq) dropwise at 0° C. under nitrogen. The mixture was then heated to reflux for 1 h and cooled to rt. Then a solution of 1-(2,3-dihydrobenzofuran-5-yl)propan-1-one (670 mg, 2.5 eq) and (4-(2-chloroethoxy)phenyl)(4-hydroxyphenyl)methanone (420 mg, 1.0 eq) in 10 mL anhydrous THF was added dropwise at 0° C. After the addition, the reaction mixture was heated to reflex for 1 h, cooled and quenched with sat. NaHCO3, filtered and the filtrate was extracted with EtOAc. The extract was dried and evaporated under reduced pressure. The residue was purified by column chromatography to give the desired product (500 mg, 78%, Z/E=1/1).

Workup

  1. temperatureThe mixture was then heated
  2. temperatureto reflux for 1 h
  3. additionAfter the addition
  4. temperaturethe reaction mixture was heated
  5. temperaturecooled
  6. customquenched with sat. NaHCO3
  7. filtrationfiltered
  8. extractionthe filtrate was extracted with EtOAc
  9. customThe extract was dried
  10. customevaporated under reduced pressure
  11. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-9fbc9cf3da504b17ba59e9b416e646d4
Source dataset
uspto-grants-2016_04
Patent number
US09309211B2

Reaction notes

Loading…