Trifluoroacetic acid → Methyl 6-(6-methoxy-2-thiophen-3-yl-1H-indol-3-ylmethyl)pyridine-2-carboxylate

HRID 2409944Notes

Reaction equation

HRID 2409944 reaction equation
C(OC([NH:8][C:9]1[CH:14]=[C:13]([O:15][CH3:16])[CH:12]=[CH:11][C:10]=1[CH:17]([C:29](=O)[C:30]1[CH:34]=[CH:33][S:32][CH:31]=1)[CH2:18][C:19]1[N:24]=[C:23]([C:25]([O:27][CH3:28])=[O:26])[CH:22]=[CH:21][CH:20]=1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH3:16][O:15][C:13]1[CH:14]=[C:9]2[C:10]([C:17]([CH2:18][C:19]3[N:24]=[C:23]([C:25]([O:27][CH3:28])=[O:26])[CH:22]=[CH:21][CH:20]=3)=[C:29]([C:30]3[CH:34]=[CH:33][S:32][CH:31]=3)[NH:8]2)=[CH:11][CH:12]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86703269Methyl 6-[2-(2-tert-butoxycarbonylamino-4-methoxyphenyl)-3-oxo-3-thiophen-3-ylpropyl]pyridine-2-carboxylate

Product 1

HCID 86703270Methyl 6-(6-methoxy-2-thiophen-3-yl-1H-indol-3-ylmethyl)pyridine-2-carboxylateYield 58.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
30 °C

Procedure

To a solution of methyl 6-[2-(2-tert-butoxycarbonylamino-4-methoxyphenyl)-3-oxo-3-thiophen-3-ylpropyl]pyridine-2-carboxylate (2.10 g) in dichloromethane (21 mL) was added dropwise trifluoroacetic acid (4.2 mL) under ice-cooling. This mixture was stirred at 30° C. overnight. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate, and this solution was washed with a saturated aqueous sodium hydrogen carbonate solution. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (938 mg). 1H-NMR (CDCl3) δ ppm: 3.86 (3H, s), 4.05 (3H, s), 4.54 (2H, s), 6.76 (1H, dd, J=2.2, 8.5 Hz), 6.90 (1H, d, J=2.2 Hz), 7.19-7.24 (1H, m), 7.28-7.35 (2H, m), 7.41 (1H, dd, J=3.0, 5.0 Hz), 7.52 (1H, dd, J=1.3, 3.0 Hz), 7.62 (1H, t, J=7.8 Hz), 7.93-7.98 (1H, m), 8.07 (1H, br s).

Workup

  1. temperaturecooling
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washthis solution was washed with a saturated aqueous sodium hydrogen carbonate solution
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane)

Sources & evidence

ORD record
ord-ffd7c7ad6453480faf7775ff12fddce3
Source dataset
uspto-grants-2014_08
Patent number
US08815903B2

Reaction notes

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