Triethyloxonium tetrafluoroborate → {(S)-1-[6-Fluoro-1-(5-fluoropyridin-3-yl)-1H-benzoimidazol-2-yl]ethyl}carbamic acid tert-butyl ester

HRID 243106Notes

Reaction equation

HRID 243106 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]=[C:29]([NH:34][C:35]2[CH:36]=[N:37][CH:38]=[C:39]([F:41])[CH:40]=2)[C:30]([NH2:33])=[CH:31][CH:32]=1>C(Cl)Cl>[C:4]([O:3][C:1](=[O:2])[NH:8][C@H:9]([C:10]1[N:34]([C:35]2[CH:36]=[N:37][CH:38]=[C:39]([F:41])[CH:40]=2)[C:29]2[CH:28]=[C:27]([F:26])[CH:32]=[CH:31][C:30]=2[N:33]=1)[CH3:11])([CH3:7])([CH3:6])[CH3:5]

Participants

5

Reactant 3

HCID 2723982Triethyloxonium tetrafluoroborateHCID 7015295Boc-Ala-NH2HCID 681580564-Fluoro-N2-(5-fluoropyridin-3-yl)benzene-1,2-diamine

Product 1

HCID 68157791{(S)-1-[6-Fluoro-1-(5-fluoropyridin-3-yl)-1H-benzoimidazol-2-yl]ethyl}carbamic acid tert-butyl esterYield 96.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of (S)-Boc-alaninamide (17.4 g, 92.5 mmol) in DCM (180 mL, dried over molecular sieves) was added triethyloxonium tetrafluoroborate (16.0 g, 84.1 mmol) in one portion under a nitrogen atmosphere. The resulting mixture was stirred at RT for 2 h. The volatiles were removed in vacuo and the resulting residue taken up in absolute EtOH (200 mL) then 4-fluoro-N2-(5-fluoropyridin-3-yl)-benzene-1,2-diamine (6.20 g, 28.0 mmol) added. After stirring the reaction mixture at 60° C. for 2 h, the solvent was removed in vacuo and the resulting residue partitioned between DCM and an aqueous solution of NaHCO3. The layers were separated and the aqueous fraction extracted with DCM. The combined organic fractions were dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (120 g Si—PCC, gradient 0-70% EtOAc in DCM) to afford the title compound as a green solid (10.1 g, 96%). LCMS (Method C): RT 3.23 min [M+H]+ 375.18.

Workup

  1. customThe volatiles were removed in vacuo
  2. stirringAfter stirring the reaction mixture at 60° C. for 2 h
  3. customthe solvent was removed in vacuo
  4. customthe resulting residue partitioned between DCM
  5. customThe layers were separated
  6. extractionthe aqueous fraction extracted with DCM
  7. dry with materialThe combined organic fractions were dried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe resulting residue was purified by column chromatography (120 g Si—PCC, gradient 0-70% EtOAc in DCM)

Sources & evidence

ORD record
ord-021a7232cc64409cb57c9978b001c468
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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