1,2-Dichloroethane → HCID 67395396, compound

HRID 1426859Notes

Reaction equation

HRID 1426859 reaction equation
FC1C([C:8]2[N:12]([S:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)(=[O:15])=[O:14])[CH:11]=[C:10]([CH2:22][N:23]([CH3:31])[C:24](=O)OC(C)(C)C)[CH:9]=2)=CC=CN=1.S(OC)(OC)(=O)=O.C([N:41]([CH2:44][CH3:45])[CH2:42]C)C.[C:46]([OH:49])(=O)[CH3:47].[Cl:50][CH2:51]CCl>C(OCC)(=O)C.C(=O)([O-])O.[Na+].C(O)C>[ClH:50].[CH3:31][N:23]([CH2:22][C:10]1[CH:9]=[C:8]([C:47]2[C:46](=[O:49])[N:41]([CH3:42])[CH:44]=[CH:45][CH:51]=2)[N:12]([S:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)(=[O:15])=[O:14])[CH:11]=1)[CH3:24]

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 176Acetic AcidHCID 6497Dimethyl SulfateHCID 8471TriethylamineHCID 67399386HCID 67399386, compound

Product 1

HCID 67395396HCID 67395396, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution (8 mL) of tert-butyl {[5-(2-fluoropyridin-3-yl)-1-(phenylsulfonyl)-1H-pyrrol-3-yl]methyl}methylcarbamate (214 mg) in 1,2-dichloroethane was added dropwise dimethyl sulfate (0.27 mL) under ice-cooling, and the mixture was stirred at 80° C. for 18 hr. The reaction mixture was cooled to room temperature, triethylamine (1.41 mL), acetic acid (0.94 mL) and ethanol (0.94 mL) were added and the mixture was heated under reflux for 2 hr. After cooling, the mixture was diluted with ethyl acetate and 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 sodium sulfate, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent: methanol-ethyl acetate=1:99→3:17) (basic TLC:Rf=0.2 (chloroform:methanol=10:1)) to give a free base of the title compound as a pale-yellow oil (yield 34.9 mg). The obtained free base (34.9 mg) was dissolved in ethyl acetate (1 mL) and ethanol (1 mL), and 4 mol/L hydrogen chloride-ethyl acetate solution (2 mL) was added. After stirring at room temperature for 2 hr, the reaction mixture was concentrated under reduced pressure. The residue was solidified with diisopropyl ether to give the title compound as a white solid (yield 20.8 mg, 11%).

Workup

  1. temperaturecooling
  2. temperatureThe reaction mixture was cooled to room temperature
  3. temperaturethe mixture was heated
  4. temperatureunder reflux for 2 hr
  5. temperatureAfter cooling
  6. extractionextracted with ethyl acetate
  7. extractionThe separated aqueous layer was extracted again with ethyl acetate
  8. washThe combined organic layer was washed with saturated brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by basic silica gel column chromatography (eluent: methanol-ethyl acetate=1:99→3:17) (basic TLC:Rf=0.2 (chloroform:methanol=10:1))

Sources & evidence

ORD record
ord-d56f53423bf74f27ad4d2e14a049186b
Source dataset
uspto-grants-2015_01
Patent number
US08933105B2

Reaction notes

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