Trifluoroacetic acid → HCID 16679129, compound

HRID 2105443Notes

Reaction equation

HRID 2105443 reaction equation
C(OC([C:6]1[N:7]([CH:26]([CH3:36])[CH2:27][NH:28][C:29]([O:31]C(C)(C)C)=O)[C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][CH:16]1[CH2:21][CH2:20][N:19]([CH:22]([CH3:24])[CH3:23])[CH2:18][CH2:17]1)=[C:10]([Br:25])[CH:9]=2)=O)C.FC(F)(F)C(O)=O.C(=O)([O-])[O-].[K+].[K+]>ClCCl.O>[Br:25][C:10]1[C:11]([O:15][CH:16]2[CH2:17][CH2:18][N:19]([CH:22]([CH3:24])[CH3:23])[CH2:20][CH2:21]2)=[CH:12][C:13]2[CH:14]=[C:6]3[C:29](=[O:31])[NH:28][CH2:27][C@@H:26]([CH3:36])[N:7]3[C:8]=2[CH:9]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 68467111HCID 68467111, compound

Product 1

HCID 16679129HCID 16679129, compoundYield 31.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

The solution of 0.21 g (0.37 mmol) 6-bromo-1-(2-tert-butoxycarbonylamino-1-methyl-ethyl)-5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid ethyl ester in 4 mL dichloromethane was cooled to 0° C. and 2 mL (2.98 g, 26.1 mmol) trifluoroacetic acid were added dropwise within 5 min. The cooling bath was removed and after 1 h the volatile components were removed at a rotary evaporator. The residue was dissolved in 4 mL methanol and 0.2 g (1.48 mmol) potassium carbonate was added under cooling. The suspension was stirred for 72 hours at room temperature and then diluted with water. The solution was extracted three times with ethyl acetate and the combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. The residue was flash-chromatographed on silica gel with a gradient of dichloromethane:methanol (100:0 to 50:50 v/v) to give 49 mg (31%) of the product as a white solid.

Workup

  1. customThe cooling bath was removed and after 1 h the volatile components
  2. customwere removed at a rotary evaporator
  3. dissolutionThe residue was dissolved in 4 mL methanol
  4. temperatureunder cooling
  5. extractionThe solution was extracted three times with ethyl acetate
  6. washthe combined organic layers were washed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was flash-chromatographed on silica gel with a gradient of dichloromethane:methanol (100:0 to 50:50 v/v)

Sources & evidence

ORD record
ord-432f5338179341ea82c4aa3f6706f516
Source dataset
uspto-grants-2009_08
Patent number
US07579351B2

Reaction notes

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