Trifluoroacetic acid → HCID 56952545, compound

HRID 1844514Notes

Reaction equation

HRID 1844514 reaction equation
CCOC(C)=O.[NH2:7][C:8]1[CH:9]=[CH:10][C:11]([O:14][C:15]2[CH:20]=[CH:19][C:18](CNC(=O)OC(C)(C)C)=[CH:17][C:16]=2[O:30][CH3:31])=[N:12][CH:13]=1.[F:32][C:33]([F:44])([F:43])[C:34]1[CH:42]=[CH:41][C:37]([C:38](Cl)=[O:39])=[CH:36][CH:35]=1.C(O)(C(F)(F)F)=O.[CH2:52]([N:54](CC)CC)C>C(Cl)Cl.O>[CH3:31][O:30][C:16]1[CH:17]=[C:18]([NH:54][CH3:52])[CH:19]=[CH:20][C:15]=1[O:14][C:11]1[N:12]=[CH:13][C:8]([NH:7][C:38](=[O:39])[C:37]2[CH:41]=[CH:42][C:34]([C:33]([F:44])([F:43])[F:32])=[CH:35][CH:36]=2)=[CH:9][CH:10]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 676074-(Trifluoromethyl)benzoyl chlorideHCID 86698877HCID 86698877, compound

Product 1

HCID 56952545HCID 56952545, compoundYield 57.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To an AcOEt (10 mL) solution of tert-butyl {4-[(5-aminopyridin-2-yl)oxy]-3-methoxyphenyl}methylcarbamate (0.60 g) and triethylamine (0.26 g) was added 4-(trifluoromethyl)benzoyl chloride (0.38 g) at 0° C. The mixture was stirred at room temperature for 1 hour. The mixture was poured into water and extracted with AcOEt. The organic layer was washed with water, saturated aqueous NaCl, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (n-hexane/AcOEt=9/1 to 7/3) to give a yellow amorphous powder. The powder was dissolved in CH2Cl2 (10 mL), then added TFA (1 mL). The mixture was stirred at room temperature for 2 hours. After removal of the solvent under reduced pressure, the residue was poured into saturated aqueous NaHCO3 and extracted with AcOEt. The organic layer was washed with water, saturated aqueous NaCl, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/AcOEt=7/3 to 3/7) to afford the title compound (0.42 g) as a colorless oil.

Workup

  1. extractionextracted with AcOEt
  2. washThe organic layer was washed with water, saturated aqueous NaCl
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by column chromatography (n-hexane/AcOEt=9/1 to 7/3)
  6. customto give a yellow amorphous powder
  7. stirringThe mixture was stirred at room temperature for 2 hours
  8. customAfter removal of the solvent under reduced pressure
  9. additionthe residue was poured into saturated aqueous NaHCO3
  10. extractionextracted with AcOEt
  11. washThe organic layer was washed with water, saturated aqueous NaCl
  12. dry with materialdried over anhydrous Na2SO4
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified by silica gel column chromatography (n-hexane/AcOEt=7/3 to 3/7)

Sources & evidence

ORD record
ord-bbd005f5b0c445a2993fed564171227b
Source dataset
uspto-grants-2015_02
Patent number
US08946437B2

Reaction notes

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