Trifluoroacetic acid → [6-Chloro-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanone

HRID 1786475Notes

Reaction equation

HRID 1786475 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[NH:17][C:18]3[C:23]([CH:24]=2)=[CH:22][C:21]([O:25][CH:26]2[CH2:31][CH2:30][N:29]([CH:32]([CH3:34])[CH3:33])[CH2:28][CH2:27]2)=[C:20]([Cl:35])[CH:19]=3)=[O:15])[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[Cl:35][C:20]1[CH:19]=[C:18]2[C:23]([CH:24]=[C:16]([C:14]([N:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)=[O:15])[NH:17]2)=[CH:22][C:21]=1[O:25][CH:26]1[CH2:27][CH2:28][N:29]([CH:32]([CH3:34])[CH3:33])[CH2:30][CH2:31]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 685649604-[6-Chloro-5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 68565620[6-Chloro-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-piperazin-1-yl-methanoneYield 94.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cold (0° C.) solution of 4-[6-chloro-5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester (example 3, 547 mg, 1.0 eq.) in dichloromethane was added trifluoroacetic acid (1.23 mL, 10 eq.) dropwise. The reaction mixture was stirred 3 h at room temperature. The mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate and a saturated aqueous sodium carbonate solution. The aqueous phase was extracted with ethyl acetate and the combined organic phases were dried over sodium sulfate, filtered and the solvents removed in vacuo. The residue was purified by flash chromatography on silica gel with a 90:9:1 dichloromethane/methanol/ammonia eluant to afford 413 mg (94%) of the title compound as a light-yellow solid.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customthe residue was partitioned between ethyl acetate
  3. extractionThe aqueous phase was extracted with ethyl acetate
  4. dry with materialthe combined organic phases were dried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvents removed in vacuo
  7. customThe residue was purified by flash chromatography on silica gel with a 90:9:1 dichloromethane/methanol/ammonia eluant

Sources & evidence

ORD record
ord-04b9f57d0cd4482a9aa02d8215ee1801
Source dataset
uspto-grants-2009_03
Patent number
US07507736B2

Reaction notes

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