Sodium hydride → (4-Iodo-pyridin-3-yl)-(2,2,2-trifluoro-ethyl)-carbamic acid tert-butyl ester

HRID 878073Notes

Reaction equation

HRID 878073 reaction equation
[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:9]=[N:10][CH:11]=[CH:12][C:13]=1[I:14])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].FC(F)(F)S(O[CH2:24][C:25]([F:28])([F:27])[F:26])(=O)=O.C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6](=[O:15])[N:7]([C:8]1[CH:9]=[N:10][CH:11]=[CH:12][C:13]=1[I:14])[CH2:24][C:25]([F:28])([F:27])[F:26])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 516892Sodium BicarbonateHCID 15366413(4-Iodo-pyridin-3-YL)-carbamic acid tert-butyl ester

Product 1

HCID 70663626(4-Iodo-pyridin-3-yl)-(2,2,2-trifluoro-ethyl)-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (4-iodo-pyridin-3-yl)-carbamic acid tert-butyl ester (280 mg, 875 μmol) in DMF (4 mL) was added NaH (42.0 mg, 962 μmol, 60% dispersion in mineral oil) at 0° C. The reaction mixture was stirred at room temperature for 30 minutes. 2,2,2-Trifluoroethyl trifluoromethanesulphonate (203 mg, 126 μL, 875 μmol, CAS RN 6226-25-1) was added and the reaction stirred at room temperature for 2 hours. The reaction mixture was poured on 30 mL 10% aqueous NaHCO3 solution and 30 mL EtOAc and the layers were separated. The aqueous layer was extracted a second time with 30 mL EtOAc and the combined organic layers were washed with 30 mL brine, dried over MgSO4, filtered and concentrated under vacuum. The compound was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:EtOAc (100:0 to 30:70). Colorless solid (207 mg, 59%). MS (ESI): m/z=403.012 [M+H]+.

Workup

  1. stirringthe reaction stirred at room temperature for 2 hours
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted a second time with 30 mL EtOAc
  4. washthe combined organic layers were washed with 30 mL brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe compound was purified by silica gel chromatography
  9. washeluting with a gradient of n-heptane:EtOAc (100:0 to 30:70)

Sources & evidence

ORD record
ord-02ba403c9a524fe59ea5036a3c9db75a
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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