Iodine → 2-Tert-butyl-3-bromo-4-iodo-6-trimethylsilylpyridine

HRID 921027Notes

Reaction equation

HRID 921027 reaction equation
[Li]CCCC.C(NC(C)C)(C)C.[C:13]([C:17]1[C:22]([Br:23])=[CH:21][CH:20]=[C:19]([Si:24]([CH3:27])([CH3:26])[CH3:25])[N:18]=1)([CH3:16])([CH3:15])[CH3:14].[I:28]I.S([O-])([O-])=O.[Na+].[Na+]>CCCCCC.C1COCC1.COC(C)(C)C.O>[C:13]([C:17]1[C:22]([Br:23])=[C:21]([I:28])[CH:20]=[C:19]([Si:24]([CH3:27])([CH3:26])[CH3:25])[N:18]=1)([CH3:16])([CH3:14])[CH3:15]

Participants

10

Reactant 5

HCID 807Iodine2×HCID 7912DiisopropylamineHCID 24437Sodium SulfiteHCID 679958492-tert-Butyl-3-bromo-6-trimethylsilylpyridineHCID 178418339Butyllithium

Product 1

HCID 679956892-Tert-butyl-3-bromo-4-iodo-6-trimethylsilylpyridine

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent4×HCID 8058HexaneSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
-78 °C

Procedure

Procedure analogous to P. N. W. Baxter, Chem. Eur. J. 2003, 9, 2531: 65.6 ml (105 mmol) of n-BuLi, 1.6 M in hexane, are added dropwise over the course of 15 min. to a vigorously stirred mixture, cooled to −78° C., of 14.0 ml (100 mmol) of diisopropylamine and 500 ml of THF. The reaction mixture is stirred at −78° C. for 45 min. and then cooled to −90° C. A solution, pre-cooled to −90° C., of 30.1 g (105 mmol) of 2-tert-butyl-3-bromo-6-trimethylsilylpyridine in 100 ml of THF is added dropwise at such a rate that the temperature does not exceed −80° C. After stirring at −90° C. for a further 1 h, the reaction mixture is warmed to −75° C., stirred at −75° C. for a further 15 min. and then re-cooled to −90° C. A solution of 30.5 g (120 mmol) of iodine in 80 ml of THF is then added dropwise at such a rate that the temperature does not exceed −75° C., the reaction mixture is stirred at −75° C. for a further 4 h and allowed to warm to room temperature. After addition of 10 ml of water and removal of the THF in vacuo, 1000 ml of tert-butyl methyl ether are added, and 100 ml of saturated sodium sulfite solution are added dropwise to the mixture in order to reduce excess iodine. The org. phase is separated off, washed three times with 300 ml of water each time, dried over sodium sulfate, the solvent is removed in vacuo, and the residue is recrystallised once from cyclohexane. Yield: 14.8 g (36 mmol), 34%. Purity: >95% according to 1H-NMR.

Workup

  1. temperaturecooled to −90° C
  2. additionis added dropwise at such a rate that the temperature
  3. customdoes not exceed −80° C
  4. stirringAfter stirring at −90° C. for a further 1 h
  5. temperaturethe reaction mixture is warmed to −75° C.
  6. stirringstirred at −75° C. for a further 15 min.
  7. temperaturere-cooled to −90° C
  8. customdoes not exceed −75° C.
  9. stirringthe reaction mixture is stirred at −75° C. for a further 4 h
  10. temperatureto warm to room temperature
  11. additionare added
  12. customphase is separated off
  13. washwashed three times with 300 ml of water each time
  14. dry with materialdried over sodium sulfate
  15. customthe solvent is removed in vacuo
  16. customthe residue is recrystallised once from cyclohexane

Sources & evidence

ORD record
ord-13af345d999942c88561f619dc19ef1f
Source dataset
uspto-grants-2016_03
Patent number
US09273080B2

Reaction notes

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