Triethylamine → Di-tert-butyl(5-bromo-3-pyridinyl)methylimidodicarbonate

HRID 601104Notes

Reaction equation

HRID 601104 reaction equation
Cl.[Br:2][C:3]1[CH:4]=[C:5]([CH2:9]Cl)[CH:6]=[NH+:7][CH:8]=1.C(N(CC)CC)C.[C:18]([NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].[K]>CN(C=O)C.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>[Br:2][C:3]1[CH:4]=[C:5]([CH2:9][N:25]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:26]([O:28][C:29]([CH3:30])([CH3:31])[CH3:32])=[O:27])[CH:6]=[N:7][CH:8]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 214777755-Bromo-3-chloromethylpyridinium hydrochlorideHCID 86222903Imidodicarbonic acid, bis(1,1-dimethylethyl) ester, potassium salt

Product 1

HCID 22265925Di-tert-butyl(5-bromo-3-pyridinyl)methylimidodicarbonateYield 60.4%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 5-bromo-3-chloromethylpyridinium hydrochloride (716 mg, 4.189 mmol) in anhydrous DMF (15 mL) under nitrogen at 0° C. was treated with triethylamine (0.65 mL, 4.61 mmol), tetrabutylammonium bromide (273 mg, 0.838 mmol), and potassium di-tert-butyl imidodicarbonate (1.284 g, 5.027 mmol). The reaction was heated to 50° C.-55° C. for 3.5 hours, then cooled to room temperature, diluted with ethyl acetate (150 mL), and washed with water (2×50 mL) and saturated aqueous sodium chloride. The combined extracts were dried over anhydrous Na2SO4, filtered, and concentrated by rotary evaporation. The residue was purified by flash column chromatography on silica gel with 6% ethyl acetate/dichloromethane to give the title compound as a colorless oil (0.980 g, 60%). MS (ESI+) m/z 387/389 (M+H)+; 1H NMR (300 MHz, CDCl3) δ 1.49 (s, 18H), 4.75 (s, 2H), 7.83 (t, J=2.02 Hz, 1H), 8.50 (d, J=1.84 Hz, 1H), 8.58 (d, J=2.21 Hz, 1H).

Workup

  1. temperatureThe reaction was heated to 50° C.-55° C. for 3.5 hours
  2. washwashed with water (2×50 mL) and saturated aqueous sodium chloride
  3. dry with materialThe combined extracts were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated by rotary evaporation
  6. customThe residue was purified by flash column chromatography on silica gel with 6% ethyl acetate/dichloromethane

Sources & evidence

ORD record
ord-1c710ae1f4d245c8a59b81ad892faa77
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

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