Trifluoroacetic acid → N-[4-(4-amino-3-fluoro-phenoxy)-2-pyridyl]cyclopropanecarboxamide

HRID 2200117Notes

Reaction equation

HRID 2200117 reaction equation
[CH:1]1([C:4]([NH:6][C:7]2[CH:12]=[C:11]([O:13][C:14]3[CH:19]=[CH:18][C:17]([NH:20]C(=O)OC(C)(C)C)=[C:16]([F:28])[CH:15]=3)[CH:10]=[CH:9][N:8]=2)=[O:5])[CH2:3][CH2:2]1.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:20][C:17]1[CH:18]=[CH:19][C:14]([O:13][C:11]2[CH:10]=[CH:9][N:8]=[C:7]([NH:6][C:4]([CH:1]3[CH2:3][CH2:2]3)=[O:5])[CH:12]=2)=[CH:15][C:16]=1[F:28]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90019939tert-butyl N-[4-[[2-(cyclopropanecarbonylamino)-4-pyridyl]oxy]-2-fluoro-phenyl]carbamate

Product 1

HCID 90020359N-[4-(4-amino-3-fluoro-phenoxy)-2-pyridyl]cyclopropanecarboxamideYield 78.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Dissolve tert-butyl N-[4-[[2-(cyclopropanecarbonylamino)-4-pyridyl]oxy]-2-fluoro-phenyl]carbamate (12.14 g, 31.28 mmol) in DCM (280 mL), add trifluoroacetic acid (35 mL). Stir the reaction at room temperature for 5 hrs. Remove the volatiles under reduced pressure. Add EtOAc (300 mL), washed with saturated NaHCO3 solution (300 mL×2), and brine (300 mL×2). Dry the organic layer with anhydrous Na2SO4. Concentrate to give the crude product. Purification by chromatography (silica gel, EtOAc:PE=1:1) affords the title compound (7 g, 78.4%). MS: (M+1): 288.

Workup

  1. customthe reaction at room temperature for 5 hrs
  2. customRemove the volatiles under reduced pressure
  3. washAdd EtOAc (300 mL), washed with saturated NaHCO3 solution (300 mL×2), and brine (300 mL×2)
  4. dry with materialDry the organic layer with anhydrous Na2SO4
  5. concentrationConcentrate
  6. customto give the crude product
  7. customPurification by chromatography (silica gel, EtOAc:PE=1:1)

Sources & evidence

ORD record
ord-a90294e835d94531b8cd22f330abb493
Source dataset
uspto-grants-2016_06
Patent number
US09359338B2

Reaction notes

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