Ethyl Acetate → HCID 86624008, compound

HRID 1426797Notes

Reaction equation

HRID 1426797 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[N:12]([S:13]([C:16]3[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=3)(=[O:15])=[O:14])[CH:11]=[C:10]([CH2:22][N:23](C)[C:24](=O)OC(C)(C)C)[C:9]=2[F:32])=[CH:6][CH:5]=[CH:4][N:3]=1.[C:33]([O:36]CC)(=[O:35])[CH3:34].Cl.[C:40]([O:43]CC)(=[O:42])[CH3:41]>CC(O)C.CO>[C:40]([OH:43])(=[O:42])/[CH:41]=[CH:34]/[C:33]([OH:36])=[O:35].[Cl:1][C:2]1[C:7]([C:8]2[N:12]([S:13]([C:16]3[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=3)(=[O:14])=[O:15])[CH:11]=[C:10]([CH2:22][NH:23][CH3:24])[C:9]=2[F:32])=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 21866389Hydrogen chloride-ethyl acetateHCID 86623995HCID 86623995, compound

Product 1

HCID 86624008HCID 86624008, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3776IsopropanolSolvent

Procedure

To a solution of tert-butyl {[5-(2-chloropyridin-3-yl)-4-fluoro-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]methyl}methylcarbamate (465 mg) in ethyl acetate (3 mL), 2-propanol (2 mL) and methanol (3 mL) was added 4 mol/L hydrogen chloride-ethyl acetate solution (6 mL), and the mixture was stirred at room temperature for 3 hr. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The separated aqueous layer was extracted again with ethyl acetate. The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent: hexane-ethyl acetate=1:1→1:9) to give a free base of the title compound as a pale-yellow oil (yield 297 mg). A solution of the obtained free base in ethyl acetate (5 mL) was added dropwise to a solution of fumaric acid (88 mg) in ethanol (5 mL) and the mixture was concentrated under reduced pressure. The residue was recrystallized from ethanol to give the title compound as a white solid (yield 267 mg, 59%).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionthe residue was diluted with saturated aqueous sodium hydrogen carbonate solution
  3. extractionextracted with ethyl acetate
  4. extractionThe separated aqueous layer was extracted again with ethyl acetate
  5. washThe combined organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by basic silica gel column chromatography (eluent: hexane-ethyl acetate=1:1→1:9)

Sources & evidence

ORD record
ord-1d14c59796b54d6bb437dd73aec6a48b
Source dataset
uspto-grants-2015_01
Patent number
US08933105B2

Reaction notes

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