Iodine → 2-Iodo-3,5-dimethoxy-4-(4-methoxy-benzyloxy)-pyridine

HRID 1258433Notes

Reaction equation

HRID 1258433 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[N:5][CH:6]=[C:7]([O:19][CH3:20])[C:8]=1[O:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=1.C([Li])(C)(C)C.[I:26]I>C1COCC1>[I:26][C:6]1[C:7]([O:19][CH3:20])=[C:8]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[C:3]([O:2][CH3:1])=[CH:4][N:5]=1

Participants

5

Reactant 3

HCID 807IodineHCID 592006313,5-Dimethoxy-4-(4-methoxy-benzyloxy)-pyridineHCID 178418306HCID 178418306, compound

Product 1

HCID 592006432-Iodo-3,5-dimethoxy-4-(4-methoxy-benzyloxy)-pyridineYield 57.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3,5-dimethoxy-4-(4-methoxy-benzyloxy)-pyridine (120 mg, 0.436 mmol) in dry THF (3 ml) at −78° C. was added t-butyllithium (0.48 mmol, 1.7 M solution in pentane) and the resulting orange mixture was stirred at low temperature for 10 minutes. A solution of iodine (166 mg, 0.654 mmol) in dry THF (2 ml) was added drop-wise and the reaction allowed to warm to room temperature and stir for 15 minutes, then quenched with 10% Na2S2O3 (aq) and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4 and concentrated onto silica-gel under reduced pressure. The solid residue was purified by flash chromatography (silica-gel, eluted with hexanes:EtOAc, 4:1) to give the product as a tan solid (100 mg, 57%). 1H-NMR (300 MHz, CDCl3) δ 7.83 (s, 1H), 7.33 (d, J=8.6 Hz, 2H), 6.86 (d, J=8.6 Hz, 2H), 5.11 (s, 2H), 3.88 (s, 3H), 3.85 (s, 3H), 3.79 (s, 3H).

Workup

  1. stirringstir for 15 minutes
  2. customquenched with 10% Na2S2O3 (aq)
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated onto silica-gel under reduced pressure
  7. customThe solid residue was purified by flash chromatography (silica-gel, eluted with hexanes:EtOAc, 4:1)

Sources & evidence

ORD record
ord-7579a3b7dec14fb591946165b293c7c2
Source dataset
uspto-grants-2013_06
Patent number
US08466163B2

Reaction notes

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