Imidazole → 3-(t-Butyldimethylsilyloxy)methyl-5-fluoromethylbenzylamine

HRID 473242Notes

Reaction equation

HRID 473242 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([CH2:11][F:12])[CH:10]=1)[CH2:6][OH:7].N1C=CN=C1.[CH3:18][C:19]([Si:22](Cl)([CH3:24])[CH3:23])([CH3:21])[CH3:20]>CN(C=O)C>[Si:22]([O:7][CH2:6][C:5]1[CH:4]=[C:3]([CH:10]=[C:9]([CH2:11][F:12])[CH:8]=1)[CH2:2][NH2:1])([C:19]([CH3:21])([CH3:20])[CH3:18])([CH3:24])[CH3:23]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 672534013-Aminomethyl-5-fluoromethylbenzylalcohol

Product 1

HCID 672543273-(t-Butyldimethylsilyloxy)methyl-5-fluoromethylbenzylamineYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-Aminomethyl-5-fluoromethylbenzylalcohol (38) (520 mg, 3.07 mmol) and imidazole (923 mg, 13.6 mmol) were dissolved in DMF (15.5 mL). The air was evacuated from the reaction system, and then Ar was charged therein. To the solution was added TBDMSCl (1.03 g, 6.83 mmol), and dissolved. Again the air was evacuated from the reaction system, and then Ar was charged therein. The mixture was stirred for 18 hours at a room temperature. TLC was used to confirm the progress of the reaction. The reaction mixture was extracted with EtOAc. The organic layer was washed with a saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to remove the solvent. The residue was purified by neutral silica gel column chromatography (hexane:EtOAc=1:1) to isolate 3-(t-butyldimethylsilyloxy)methyl-5-fluoromethylbenzylamine (41) (661 mg, 76%) as a colorless oil.

Workup

  1. customThe air was evacuated from the reaction system
  2. additionAr was charged
  3. dissolutiondissolved
  4. customAgain the air was evacuated from the reaction system
  5. additionAr was charged
  6. customthe progress of the reaction
  7. extractionThe reaction mixture was extracted with EtOAc
  8. washThe organic layer was washed with a saturated sodium chloride aqueous solution
  9. dry with materialdried over anhydrous sodium sulfate
  10. customevaporated under reduced pressure
  11. customto remove the solvent
  12. customThe residue was purified by neutral silica gel column chromatography (hexane:EtOAc=1:1)

Sources & evidence

ORD record
ord-749de42572ca4e5e8fa57d09d7123dcb
Source dataset
uspto-grants-2014_01
Patent number
US08633304B2

Reaction notes

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