Benzyl Bromide → 2-(Benzyloxy)-4-ethoxy-5-iodopyridine

HRID 1050135Notes

Reaction equation

HRID 1050135 reaction equation
[CH2:1]([O:3][C:4]1[C:9]([I:10])=[CH:8][N:7]=[C:6]([OH:11])[CH:5]=1)[CH3:2].Br[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C1COCC1.C(=O)([O-])[O-].[Ag+2]>[CH2:13]([O:11][C:6]1[CH:5]=[C:4]([O:3][CH2:1][CH3:2])[C:9]([I:10])=[CH:8][N:7]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 2

HCID 7498Benzyl BromideHCID 178467033HCID 178467033, compound

Product 1

HCID 904176602-(Benzyloxy)-4-ethoxy-5-iodopyridineYield 76.2%

Reagents, catalysts & solvents 2

HCID 178418647HCID 178418647, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

To a mixture of 4-ethoxy-5-iodopyridin-2-ol (3.7 g, 13.96 mmol) in THF (10 mL) was added (bromomethyl)benzene (2.87 g, 16.75 mmol) and silver carbonate (7.70 g, 27.9 mmol). The mixture was stirred at 70° C. for 16 h. The reaction residue was then filtered and the filtrate was concentrated. The mixture was diluted with water (30 mL) and extracted with DCM (30 mL×2). The combined organic extract was washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=5:1). All fractions found to contain product by TLC (PE/EA=5:1, Rf=0.6) were combined and concentrated to yield a light yellow oil of 2-(benzyloxy)-4-ethoxy-5-iodopyridine (4.2 g, 10.64 mmol, 76% yield). 1H NMR (400 MHz, MeOH-d4) δ 8.25 (s, 1H), 7.47-7.41 (m, 2H), 7.40-7.30 (m, 3H), 6.41 (s, 1H), 5.32 (s, 2H), 4.16 (q, J=7.2 Hz, 2H), 1.47 (t, J=7.2 Hz, 3H); ES-LCMS m/z 356.0 (M+H).

Workup

  1. filtrationThe reaction residue was then filtered
  2. concentrationthe filtrate was concentrated
  3. additionThe mixture was diluted with water (30 mL)
  4. extractionextracted with DCM (30 mL×2)
  5. extractionThe combined organic extract
  6. washwas washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material was purified by silica column chromatography (PE/EA=5:1)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-88bbf6addbe345ff9db0a3ee78161033
Source dataset
uspto-grants-2016_07
Patent number
US09382238B2

Reaction notes

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