Ethyl Acetate → HCID 67398171, compound

HRID 1426808Notes

Reaction equation

HRID 1426808 reaction equation
[F:1][C:2]1[C:3]([CH2:25][N:26](C)[C:27](=O)OC(C)(C)C)=[CH:4][N:5]([S:14]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([CH2:23][OH:24])[CH:18]=2)(=[O:16])=[O:15])[C:6]=1[C:7]1[C:8]([F:13])=[N:9][CH:10]=[CH:11][CH:12]=1.[C:35]([O:38]CC)(=[O:37])[CH3:36].Cl.[C:42]([O:45]CC)(=[O:44])[CH3:43]>CC(O)C>[C:42]([OH:45])(=[O:44])/[CH:43]=[CH:36]/[C:35]([OH:38])=[O:37].[C:35]([O:24][CH2:23][C:19]1[CH:20]=[CH:21][CH:22]=[C:17]([S:14]([N:5]2[CH:4]=[C:3]([CH2:25][NH:26][CH3:27])[C:2]([F:1])=[C:6]2[C:7]2[C:8]([F:13])=[N:9][CH:10]=[CH:11][CH:12]=2)(=[O:16])=[O:15])[CH:18]=1)(=[O:37])[CH3:36]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 21866389Hydrogen chloride-ethyl acetateHCID 67399475HCID 67399475, compound

Product 1

HCID 67398171HCID 67398171, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a solution of tert-butyl [(4-fluoro-5-(2-fluoropyridin-3-yl)-1-{[3-(hydroxymethyl)phenyl]sulfonyl}-1H-pyrrol-3-yl)methyl]methylcarbamate (207 mg) in ethyl acetate (3 mL) and 2-propanol (2 mL) was added 4 mol/L hydrogen chloride-ethyl acetate solution (6 mL), and the mixture was stirred at room temperature for 2 hr. The solvent was concentrated under reduced pressure, diluted with ethyl acetate, and washed with saturated aqueous sodium hydrogen carbonate solution. 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=4:1→ethyl acetate:methanol=32:1) (basic TLC:Rf=0.4 (ethyl acetate)) to give a free base of the title compound as a pale-yellow oil (yield 61.1 mg). A solution of the obtained free base in ethyl acetate (1 mL) was added dropwise to a solution of fumaric acid (16 mg) in ethanol (1 mL) and the mixture was concentrated under reduced pressure. The residue was recrystallized from a mixed solvent of ethyl acetate and ethanol to give the title compound as a white solid (yield 58 mg, 25%).

Workup

  1. concentrationThe solvent was concentrated under reduced pressure
  2. additiondiluted with ethyl acetate
  3. washwashed with saturated aqueous sodium hydrogen carbonate solution
  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=4:1→ethyl acetate:methanol=32:1) (basic TLC:Rf=0.4 (ethyl acetate))

Sources & evidence

ORD record
ord-dbbf85064dd34268b99b6bb0e34feee3
Source dataset
uspto-grants-2015_01
Patent number
US08933105B2

Reaction notes

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