Triethyloxonium tetrafluoroborate → Acetic acid 2-((S)-1-tert-butoxycarbonylaminoethyl)-5-fluoro-3-phenyl-3H-benzoimidazol-4-ylmethyl ester

HRID 243252Notes

Reaction equation

HRID 243252 reaction equation
[C:1]([O:5][C:6](=[O:13])[NH:7][C@H:8]([C:10](=O)[NH2:11])[CH3:9])([CH3:4])([CH3:3])[CH3:2].F[B-](F)(F)F.C([O+](CC)CC)C.N[C:27]1[C:28]([NH:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)=[C:29]([C:35]([F:38])=[CH:36][CH:37]=1)[CH2:30][O:31][C:32](=[O:34])[CH3:33]>C(Cl)Cl>[C:1]([O:5][C:6]([NH:7][C@H:8]([C:10]1[N:39]([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:28]2[C:29]([CH2:30][O:31][C:32](=[O:34])[CH3:33])=[C:35]([F:38])[CH:36]=[CH:37][C:27]=2[N:11]=1)[CH3:9])=[O:13])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 2723982Triethyloxonium tetrafluoroborateHCID 7015295Boc-Ala-NH2HCID 68158130Acetic acid 3-amino-6-fluoro-2-phenylaminobenzyl ester

Product 1

HCID 68157763Acetic acid 2-((S)-1-tert-butoxycarbonylaminoethyl)-5-fluoro-3-phenyl-3H-benzoimidazol-4-ylmethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of ((S)-1-carbamoylethyl)carbamic acid tert-butyl ester 3.94 g, 20.9 mmol) in DCM (20 mL) was added triethyloxonium tetrafluoroborate (3.35 g, 17.6 mmol) and the reaction mixture stirred at RT for 2 hours, during which the solids dissolved. The reaction mixture was concentrated in vacuo and the residue dissolved in ethanol (20 mL). Acetic acid 3-amino-6-fluoro-2-phenylaminobenzyl ester (2.3 g, 8.38 mmol) was added and the reaction heated at 75° C. for 1 h. The reaction mixture was concentrated in vacuo, the residue dissolved in water and the product extracted with EtOAc (3×20 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 give the title compound as an off white solid. LCMS (Method C): RT=3.37 min, [M+H-tBu]+=372, 100%, [M+H]+=428, 40%.

Workup

  1. dissolutiondissolved
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionthe residue dissolved in ethanol (20 mL)
  4. temperaturethe reaction heated at 75° C. for 1 h
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. dissolutionthe residue dissolved in water
  7. extractionthe product extracted with EtOAc (3×20 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-acc0c87a77e24427a205c3c766db123a
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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