Iodine → 2-Benzyloxy-6-iodo-3-methoxy-phenol

HRID 1042565Notes

Reaction equation

HRID 1042565 reaction equation
[CH2:1]([O:8][C:9]1[C:14]([O:15][CH3:16])=[CH:13][CH:12]=[CH:11][C:10]=1[OH:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[I:18]I>C(O)(=O)C>[CH2:1]([O:8][C:9]1[C:14]([O:15][CH3:16])=[CH:13][CH:12]=[C:11]([I:18])[C:10]=1[OH:17])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 807IodineHCID 143174112-Benzyloxy-3-methoxy-phenol

Product 1

HCID 574219402-Benzyloxy-6-iodo-3-methoxy-phenolYield 48.5%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
55 °C

Procedure

To a suspension of 2-benzyloxy-3-methoxy-phenol (3.80 g, 16.5 mmol) and cupric acetate monohydrate (3.28 g, 16.5 mmol) in acetic acid (45 mL) was added iodine (4.62 g, 18.2 mmol) and the reaction was heated to 55° C. and stirred overnight. After this time the reaction was quenched with 10% aqueous sodium thiosulphate (40 mL) and diluted with diethyl ether (150 mL). The resultant emulsion was filtered through celite and the organic layer was washed with water (4×40 mL) and brine (40 mL), dried over magnesium sulphate and the solvent removed under vacuum. The crude residue was purified by silica-gel flash chromatography (sequential elution—5% diethyl ether in hexane, 10%). Concentration of fractions containing the pure product as indicated by thin layer chromatography gave 2.85 g of the desired product. Later impure fractions were combined and re-chromatographed to yield a further 520 mg of material (combined mass=3.37 g, 57% yield). 1H-NMR (CDCl3) δ 7.40-7.33 (m, 5H), 7.34 (d, J=8.9 Hz, 1H), 6.34 (d, J=8.9 Hz, 1H), 6.06 (s, 1H), 5.06 (s, 2H), 3.86 (s, 3H).

Workup

  1. customAfter this time the reaction was quenched with 10% aqueous sodium thiosulphate (40 mL)
  2. additiondiluted with diethyl ether (150 mL)
  3. filtrationThe resultant emulsion was filtered through celite
  4. washthe organic layer was washed with water (4×40 mL) and brine (40 mL)
  5. dry with materialdried over magnesium sulphate
  6. customthe solvent removed under vacuum
  7. customThe crude residue was purified by silica-gel flash chromatography (sequential elution—5% diethyl ether in hexane, 10%)
  8. additionConcentration of fractions containing the pure product

Sources & evidence

ORD record
ord-ea3d7c5ff7e3472a81e717a4b9d80e2b
Source dataset
uspto-grants-2013_10
Patent number
US08557982B2

Reaction notes

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