Ethyl Acetate → 3-[4-(4-Acetyl-3-hydroxy-2-iodo-phenoxymethyl)-benzyl]-benzoic acid methyl ester

HRID 1161133Notes

Reaction equation

HRID 1161133 reaction equation
C(=O)([O-])[O-].[K+].[K+].[C:7]([C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[C:12]([I:17])[C:11]=1[OH:18])(=[O:9])[CH3:8].[CH3:19][O:20][C:21](=[O:37])[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([CH2:35]I)=[CH:31][CH:30]=2)[CH:23]=1.C(OCC)(=O)C>CC(C)=O.ClCCl>[CH3:19][O:20][C:21](=[O:37])[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH2:28][C:29]2[CH:30]=[CH:31][C:32]([CH2:35][O:16][C:13]3[CH:14]=[CH:15][C:10]([C:7](=[O:9])[CH3:8])=[C:11]([OH:18])[C:12]=3[I:17])=[CH:33][CH:34]=2)[CH:23]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 132755071-(2,4-Dihydroxy-3-iodophenyl)ethan-1-oneHCID 574383993-(4-Iodomethyl-benzyl)-benzoic acid methyl ester

Product 1

HCID 666995233-[4-(4-Acetyl-3-hydroxy-2-iodo-phenoxymethyl)-benzyl]-benzoic acid methyl esterYield 61%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

Potassium carbonate (675 mg, 4.88 mmol) is added to a solution of 4-acetyl-3-hydroxy-2-iodo-phenol (925 mg, 3.33 mmol) and 3-(4-iodomethyl-benzyl)-benzoic acid methyl ester (1.21 g, 3.30 mmol) in acetone (65 mL). The resulting suspension is heated at 50° C. for 16 hours. The reaction mixture is cooled to room temperature and concentrated in vacuo. The residue is taken up in dichloromethane, washed with 1N hydrochloric acid, brine, dried over magnesium sulfate, filtered and concentrated to give a yellow solid. This solid is dissolved in dichloromethane and a white precipitate forms upon addition of ethyl acetate. The white solid is filtered off and the mother liquor is purified by flash chromatography, eluting with 20% ethyl acetate in hexanes. The precipitate and chromatographed materials are combined to give 1.04 g of the title compound as a pale yellow solid: MS (m/z) 517 (M+1), 515 (M−1); 1H NMR δ (CDCl3); 13.58 (s, 1H), 7.93 (m, 2H), 7.74 (d, J=9.0 Hz, 1H), 7.45-7.38 (m, 4H), 7.25 (d, J=8.0 Hz, 2H), 6.50 (d, J=9.0 Hz, 1H), 5.27 (s, 2H), 4.07 (s, 2H), 3.94 (s, 3H), 2.63 (s, 3H).

Workup

  1. temperatureThe reaction mixture is cooled to room temperature
  2. concentrationconcentrated in vacuo
  3. washwashed with 1N hydrochloric acid, brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a yellow solid
  8. filtrationThe white solid is filtered off
  9. customthe mother liquor is purified by flash chromatography
  10. washeluting with 20% ethyl acetate in hexanes
  11. customThe precipitate and chromatographed materials

Sources & evidence

ORD record
ord-9e0c0c18037747bea4ce55ba9e4e58b6
Source dataset
uspto-grants-2010_10
Patent number
US07816523B2

Reaction notes

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