Acetic Acid → 5-[6-(1-Hydroxy-1-methylethyl)pyridin-3-yl]-2-nitrothiophene-3-carboxamide

HRID 385736Notes

Reaction equation

HRID 385736 reaction equation
[Si]([O:8][C:9]([C:12]1[N:17]=[CH:16][C:15]([C:18]2[S:22][C:21]([N+:23]([O-:25])=[O:24])=[C:20]([C:26]([NH2:28])=[O:27])[CH:19]=2)=[CH:14][CH:13]=1)([CH3:11])[CH3:10])(C(C)(C)C)(C)C.CC(O)=O.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.O>[OH:8][C:9]([C:12]1[N:17]=[CH:16][C:15]([C:18]2[S:22][C:21]([N+:23]([O-:25])=[O:24])=[C:20]([C:26]([NH2:28])=[O:27])[CH:19]=2)=[CH:14][CH:13]=1)([CH3:11])[CH3:10]

Participants

6

Reactant 3

HCID 176Acetic Acid2×HCID 2724141Tetrabutylammonium Fluoride2×HCID 595256065-[6-(1-{[tert-Butyl(dimethyl)silyl]oxy}-1-methylethyl)pyridin-3-yl]-2-nitrothiophene-3-carboxamide

Product 1

HCID 595258015-[6-(1-Hydroxy-1-methylethyl)pyridin-3-yl]-2-nitrothiophene-3-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 5-[6-(1-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyl)pyridin-3-yl]-2-nitrothiophene-3-carboxamide (665 mg, 1.58 mmol) in THF (10 mL) were added AcOH (0.36 ml, 6.13 mmol) and TBAF (1.0 M in THF, 6.31 mL, 6.31 mmol). The sealed reaction was stirred at 90° C. for 18 h. Additional AcOH (0.361 ml, 6.13 mmol) and TBAF (6.31 mL, 6.31 mmol) were added, and the reaction was stirred at 90° C. for another 24 h. The brown solution was cooled to room temperature, diluted with water, and extracted with EtOAc (2×). The combined organic extracts were washed with brine (2×), dried (MgSO4), filtered, and evaporated. Flash chromatography of the crude residue (50-100% EtOAc/hexanes) provided a yellow residue that was triturated with Et2O and filtered to isolate the title compound as a yellow solid.

Workup

  1. customThe sealed reaction
  2. stirringthe reaction was stirred at 90° C. for another 24 h
  3. temperatureThe brown solution was cooled to room temperature
  4. extractionextracted with EtOAc (2×)
  5. washThe combined organic extracts were washed with brine (2×)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customFlash chromatography of the crude residue (50-100% EtOAc/hexanes) provided a yellow residue that
  10. customwas triturated with Et2O
  11. filtrationfiltered

Sources & evidence

ORD record
ord-ec7bf98dcf244e28a98332a654b66ff2
Source dataset
uspto-grants-2013_02
Patent number
US08367706B2

Reaction notes

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