Bicarbonate Ion → Di(tert-butyl) 4-fluoro-2-iodobenzylimidodicarbonate

HRID 2252808Notes

Reaction equation

HRID 2252808 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][C:4]=1[I:10].[H-].[Na+].[NH:13]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15].C(=O)(O)[O-]>CN(C=O)C.O>[F:9][C:6]1[CH:7]=[CH:8][C:3]([CH2:2][N:13]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])=[C:4]([I:10])[CH:5]=1

Participants

7

Reactant 4

HCID 769Bicarbonate IonHCID 24758Sodium hydrideHCID 279800Di-tert-butyl IminodicarboxylateHCID 128060541-(Bromomethyl)-4-fluoro-2-iodobenzene

Product 1

HCID 59645217Di(tert-butyl) 4-fluoro-2-iodobenzylimidodicarbonate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

A solution of 1-(bromomethyl)-4-fluoro-2-iodobenzene (Example 3, step 1) (5 g, 15.9 mmol) in dry DMF (50 mL) under argon was cooled to 2° C. and treated with NaH (60% dispersion in oil, 0.4 g, 17.5 mmol) and stirred for 5 minutes to give a fine slurry. A solution of di-tert-butyl iminodicarboxylate (Aldrich, 3.8 g, 17.5 mmol) in 20 ml dry DMF was added dropwise, keeping the temperature between 2 and 7° C. After stirring for 1 hr at 0° C., the solution was allowed to warm to room temperature and stirred overnight. The reaction was poured into bicarbonate solution and water was added until all the solids dissolved. The solution wag extracted with ether and the combined organic layers were dried over Na2SO4, filtered and evaporated and the crude product was purified on 120 g silica gel ISCO cartridge eluting first with a gradient of 0-5% EtOAc/Hexanes followed by a gradient of 5-10% EtOAc/Hexanes to give the product as a clear oil that solidified to a white solid.

Workup

  1. customto give a fine slurry
  2. customthe temperature between 2 and 7° C
  3. stirringAfter stirring for 1 hr at 0° C.
  4. stirringstirred overnight
  5. additionwas added until all the solids
  6. dissolutiondissolved
  7. extractionThe solution wag extracted with ether
  8. dry with materialthe combined organic layers were dried over Na2SO4
  9. filtrationfiltered
  10. customevaporated
  11. customthe crude product was purified on 120 g silica gel ISCO cartridge
  12. washeluting first with a gradient of 0-5% EtOAc/Hexanes

Sources & evidence

ORD record
ord-bb915c781e924e55b614962a056afbe5
Source dataset
uspto-grants-2008_01
Patent number
US07323460B2

Reaction notes

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