Acetyl chloride → 1-[5-Hydroxy-2-(4-hydroxy-phenyl)-benzofuran-3-yl]-ethanone

HRID 1794530Notes

Reaction equation

HRID 1794530 reaction equation
CC(C)(C)C([O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[O:13][C:14]3[CH:20]=[CH:19][C:18]([O:21]C(=O)C(C)(C)C)=[CH:17][C:15]=3[CH:16]=2)=[CH:8][CH:7]=1)=O.[C:30](Cl)(=[O:32])[CH3:31].[Al+3].[Cl-].[Cl-].[Cl-].CCOC(C)=O>C(Cl)Cl.CO.C1COCC1>[OH:21][C:18]1[CH:19]=[CH:20][C:14]2[O:13][C:12]([C:9]3[CH:8]=[CH:7][C:6]([OH:5])=[CH:11][CH:10]=3)=[C:16]([C:30](=[O:32])[CH3:31])[C:15]=2[CH:17]=1

Participants

7

Reactant 4

HCID 6367Acetyl chlorideHCID 8857Ethyl AcetateHCID 6451240Aluminum(III) ChlorideHCID 235173722,2-Dimethyl-propionic acid 2-[4-(2,2-dimethyl-propionyloxy)-phenyl]-benzofuran-5-yl ester

Product 1

HCID 222216281-[5-Hydroxy-2-(4-hydroxy-phenyl)-benzofuran-3-yl]-ethanone

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A solution of the bis-pivaloylate 109 (1 g, 2.54 mmol) in CH2Cl2 was treated with acetyl chloride (0.22 g, 2.8 mmol) was treated with AlCl3 (0.36 g, 2.8 mmol) and stirred at rt overnight. The reaction was worked up by adding EtOAc, washing with 2 N HCl aq, saturated NaHCO3 aq and drying over MgSO4. After filtering and concentrating, the residue was chromatographed on silica gel (EtOAc/hexanes 1:4 to EtOAc/hexanes 1:1) to yield the product which was promptly dissolved in MeOH/THF/2 N NaOH aq and warmed until TLC analysis indicated that the hydrolysis of the pivalate esters was completed. The reaction was concentrated to remove the organic solvents and the residue aqueous was acidified with 2 N HCl aq and extracted with EtOAc. The EtOAc extract was washed with saturated NaHCO3 solution, brine and dried over MgSO4. After filtration and concentration, the residue was chromatographed on silica gel (EtOAc/hexanes 1:4 to EtOAc/hexanes 1:1) to yield 90 mg of the desired pdt: Mp=243–251° C.; 1H NMR (DMSO-d6) δ 10.08 (br s, 1 H), 9.40 (br s, 1 H), 7.63 (d, 2 H, J=8.8 Hz), 7.43 (d, 1 H, d=9.3 Hz), 7.41 (d, 1 H, J=2.4 Hz), 6.92 (d, 2 H, J=8.8 Hz), 6.80 (dd, 1 H, J=8.8 Hz, 2.4 Hz), 2.26 (s, 3 H).

Workup

  1. washwashing with 2 N HCl aq, saturated NaHCO3 aq
  2. dry with materialdrying over MgSO4
  3. filtrationAfter filtering
  4. concentrationconcentrating
  5. customthe residue was chromatographed on silica gel (EtOAc/hexanes 1:4 to EtOAc/hexanes 1:1)
  6. customto yield the product which
  7. temperaturewarmed until TLC analysis
  8. concentrationThe reaction was concentrated
  9. customto remove the organic solvents
  10. extractionextracted with EtOAc
  11. extractionThe EtOAc extract
  12. washwas washed with saturated NaHCO3 solution, brine
  13. dry with materialdried over MgSO4
  14. filtrationAfter filtration and concentration
  15. customthe residue was chromatographed on silica gel (EtOAc/hexanes 1:4 to EtOAc/hexanes 1:1)
  16. customto yield 90 mg of the desired pdt

Sources & evidence

ORD record
ord-034d59c268ae465bb3f483e171dfb4f9
Source dataset
uspto-grants-2006_04
Patent number
US07022733B2

Reaction notes

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