Tetrabutylammonium Fluoride → HCID 90421732, compound

HRID 1054893Notes

Reaction equation

HRID 1054893 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([Cl:25])=[C:11]([C:14]3[C:15]([O:23][CH3:24])=[N:16][C:17]([N:20]([CH3:22])[CH3:21])=[CH:18][CH:19]=3)[CH:12]=2)[N:7](S(C2C=CC(C)=CC=2)(=O)=O)[CH:6]=1)=[O:4].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.C(OCC)(=O)C>[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([Cl:25])=[C:11]([C:14]3[C:15]([O:23][CH3:24])=[N:16][C:17]([N:20]([CH3:21])[CH3:22])=[CH:18][CH:19]=3)[CH:12]=2)[NH:7][CH:6]=1)=[O:4]

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 90421710HCID 90421710, compound

Product 1

HCID 90421732HCID 90421732, compoundYield 94.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of Intermediate 6-chloro-5-(6-dimethylamino-2-methoxy-pyridin-3-yl)-1-(toluene-4-sulfonyl)-1H-indole-3-carboxylic acid methyl ester (109 g, 212 mmol) in THF (1000 mL) at room temperature was added tetrabutylammonium fluoride (1.0 M in THF, 400 mL, 400 mmol). The reaction was stirred at reflux for 3 h before cooling to room temperature and diluting with ethyl acetate (2000 mL). This was washed with sat. aq. NaHCO3 (2×750 mL), sat. aq. NH4Cl (2×750 mL), water (750 mL), and brine (750 mL), and then dried over MgSO4, filtered, and concentrated in vacuo. The residue was triturated with methanol (˜500 mL) and filtered. The solids were washed with methanol (300 mL) and suction dried overnight to afford desired product (71.8 g, 94%) as a white solid. 1H NMR (DMSO-d6, 400 MHz) δ=11.99 (s, 1 H) 8.13 (s, 1 H) 7.82 (s, 1 H) 7.57 (s, 1 H) 7.32 (d, J=8.20 Hz, 1 H) 6.22 (d, J=8.20 Hz, 1 H) 3.78 (s, 3 H) 3.76 (s, 3 H) 3.07 (s, 6 H); MS (ES+) 360.1 (M+H)+.

Workup

  1. temperatureat reflux for 3 h
  2. washThis was washed with sat. aq. NaHCO3 (2×750 mL), sat. aq. NH4Cl (2×750 mL), water (750 mL), and brine (750 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was triturated with methanol (˜500 mL)
  7. filtrationfiltered
  8. washThe solids were washed with methanol (300 mL) and suction
  9. customdried overnight

Sources & evidence

ORD record
ord-709beb2a2e0b443c94ee2aeae04c7200
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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