Triethyloxonium tetrafluoroborate → [(S)-1-(6-Fluoro-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tert-butyl ester

HRID 243008Notes

Reaction equation

HRID 243008 reaction equation
[C:1]([NH:8][C@H:9]([C:11](N)=O)[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].F[B-](F)(F)F.C([O+](CC)CC)C.[F:26][C:27]1[CH:28]=[CH:29][C:30]([N+:40]([O-])=O)=[C:31]([NH:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][N:35]=2)[CH:32]=1>C(Cl)Cl>[C:4]([O:3][C:1](=[O:2])[NH:8][C@H:9]([C:10]1[N:33]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][N:35]=2)[C:31]2[CH:32]=[C:27]([F:26])[CH:28]=[CH:29][C:30]=2[N:40]=1)[CH3:11])([CH3:7])([CH3:6])[CH3:5]

Participants

5

Reactant 3

HCID 2723982Triethyloxonium tetrafluoroborateHCID 7015295Boc-Ala-NH2HCID 68157116(5-Fluoro-2-nitrophenyl)pyridin-2-yl-amine

Product 1

HCID 68157940[(S)-1-(6-Fluoro-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tert-butyl esterYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(Prep 2) To a suspension of (S)-Boc-alaninamide (79.4 g, 0.42 mol) in DCM (750 mL) was added triethyloxonium tetrafluoroborate (69.5 g, 0.37 mol) and the reaction mixture stirred at RT for 2 h, during which the solids dissolved. The reaction mixture was concentrated in vacuo and the residue dissolved in ethanol (750 mL). (5-Fluoro-2-nitrophenyl)pyridin-2-yl-amine (57.1 g, 0.28 mol) was added and the reaction heated at 70° C. for 1 h. The reaction mixture was concentrated in vacuo, the residue dissolved in water and the product extracted with EtOAc (3×150 mL). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, eluting with 0-100% EtOAc in cyclohexane) to yield the title compound as a white foam (60.3 mg, 60%).

Workup

  1. dissolutiondissolved
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionthe residue dissolved in ethanol (750 mL)
  4. temperaturethe reaction heated at 70° C. for 1 h
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. dissolutionthe residue dissolved in water
  7. extractionthe product extracted with EtOAc (3×150 mL)
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated in vacuo
  11. washThe resultant residue was subjected to flash chromatography (SiO2, eluting with 0-100% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-212c9ce0f6d04f0a824f1b10be44bf11
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

Loading…