Ethanol → HCID 178505398, compound

HRID 547654Notes

Reaction equation

HRID 547654 reaction equation
[CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH:2]1[N:10]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][C:26]2[CH:31]=[C:30]([NH:32][C:33](=[O:38])[C:34]([F:37])([F:36])[F:35])[C:29]([N+:39]([O-])=O)=[CH:28][C:27]=2[F:42])=[CH:21][CH:20]=1)C(=O)OC(C)(C)C.C([OH:45])C>[Pd]>[F:35][C:34]([F:37])([F:36])[C:33]([OH:38])=[O:45].[F:42][C:27]1[C:26]([O:25][C:22]2[CH:23]=[CH:24][C:19]([CH2:18][NH:10][CH:2]3[CH2:1][C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[CH2:3]3)=[CH:20][CH:21]=2)=[CH:31][C:30]2[NH:32][C:33]([C:34]([F:37])([F:36])[F:35])=[N:39][C:29]=2[CH:28]=1

Participants

4

Reactant 2

HCID 702EthanolHCID 57585989HCID 57585989, compound

Product 1

HCID 178505398HCID 178505398, compound

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

To an ethanol (3 mL) solution of the crude 1,1-dimethylethyl 2,3-dihydro-1H-inden-2-yl{[4-({2-fluoro-4-nitro-5-[(trifluoroacetyl)amino]phenyl}oxy)phenyl]methyl}carbamate (0.375 g, 0.636 mmol) was added 10% palladium on carbon (0.076 g) and the reaction mixture was subjected to hydrogenation under an atmosphere of hydrogen. The reaction mixture was stirred for 4 hours and the catalyst removed by filtration through Celite. The filtrate was concentrated and the residue re-dissolved in glacial acetic acid (3 mL) and heated to 60 degrees Centigrade for 1 hour, cooled, concentrated and azeotroped several times with toluene/CH2Cl2. The residue was dissolved in CH2Cl2 and trifluoroacetic acid added. The reaction mixture was stirred for 16 hours and then concentrated. Purification of the final compound was accomplished by preparative HPLC to afford N-[(4-{[5-Fluoro-2-(trifluoromethyl)-1H-benzimidazol-6-yl]oxy}phenyl)methyl]-2,3-dihydro-1H-inden-2-amine trifluoroacetate (Example No. 100).

Workup

  1. customthe catalyst removed by filtration through Celite
  2. concentrationThe filtrate was concentrated
  3. dissolutionthe residue re-dissolved in glacial acetic acid (3 mL)
  4. temperatureheated to 60 degrees Centigrade for 1 hour
  5. temperaturecooled
  6. concentrationconcentrated
  7. customazeotroped several times with toluene/CH2Cl2
  8. dissolutionThe residue was dissolved in CH2Cl2
  9. additiontrifluoroacetic acid added
  10. stirringThe reaction mixture was stirred for 16 hours
  11. concentrationconcentrated
  12. customPurification of the final compound

Sources & evidence

ORD record
ord-35465ffff8594fbcabde8fafbe33715e
Source dataset
uspto-grants-2011_05
Patent number
US07939528B2

Reaction notes

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