Iodine → 2-Iodo-6-methoxynaphthalene

HRID 1254182Notes

Reaction equation

HRID 1254182 reaction equation
C([Li])CCC.Br[C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:17][CH3:18])[CH:13]=2)[CH:8]=1.[I:19]I.O>C1COCC1>[I:19][C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:17][CH3:18])[CH:13]=2)[CH:8]=1

Participants

6

Reactant 4

HCID 807Iodine2×HCID 962WaterHCID 787862-Bromo-6-methoxynaphthaleneHCID 178418339Butyllithium

Product 1

HCID 3490672-Iodo-6-methoxynaphthalene

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-75 °C

Procedure

n-Butyllithium (2.5 M in hexanes, 92 mL, 230 mmol) is added via dropping funnel to a solution of 2-bromo-6-methoxy-naphthalene (49.5 g, 209 mmol) in anhydrous THF (2 L) at −75° C. at such a rate that the temperature is kept below −70° C. (over 45 min). The resulting yellow solution is stirred for 15 min at −75° C. A solution of iodine (58.3 g, 230 mmol) in anhydrous THF (100 mL) is added via a fresh dropping funnel until the red iodine colour persists (addition over 45 min, max. temp. −68° C.). The mixture is warmed to rt. and water (1.3 L) is added. The mixture is extracted with dichloromethane (2 L) with brine (500 mL) being added to aid the separation. The aqueous fraction is back-extracted with dichloromethane (1 L). The combined organic fractions are reduced in vacuo to approx. 1 L, washed with saturated aqueous sodium metabisulphite (100 mL), then brine (200 mL), dried (Na2SO4), filtered and solvent removed in vacuo. The crude residue is recrystalised from IMS (1.9 l) washing with ice-cold IMS (2×150 mL) and dried in a vacuum oven at 70, ° C. to give a light cream crystalline solid. 46.45 g, 78%.

Workup

  1. customat −75° C.
  2. customis kept below −70° C.
  3. custom(over 45 min)
  4. temperatureThe mixture is warmed to rt
  5. extractionThe mixture is extracted with dichloromethane (2 L) with brine (500 mL)
  6. additionbeing added
  7. customthe separation
  8. extractionThe aqueous fraction is back-extracted with dichloromethane (1 L)
  9. washwashed with saturated aqueous sodium metabisulphite (100 mL)
  10. dry with materialbrine (200 mL), dried (Na2SO4)
  11. filtrationfiltered
  12. customsolvent removed in vacuo
  13. customThe crude residue is recrystalised from IMS (1.9 l)
  14. washwashing with ice-cold IMS (2×150 mL)
  15. customdried in a vacuum oven at 70, ° C
  16. customto give a light cream crystalline solid

Sources & evidence

ORD record
ord-f16069d0f0ee4c61b1e805f326e1f277
Source dataset
uspto-grants-2013_06
Patent number
US08455563B2

Reaction notes

Loading…