Hydrochloric Acid → tert-butyl {[1-[(5-acetyl-2-furyl)sulfonyl]-4-fluoro-5-(2-fluoropyridin-3-yl)-1H-pyrrol-3-yl]methyl}methylcarbamate

HRID 1426743Notes

Reaction equation

HRID 1426743 reaction equation
[F:1][C:2]1[C:3]([CH2:25][N:26]([CH3:34])[C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:4][N:5]([S:14]([C:17]2[O:18][C:19]([CH:22]([OH:24])[CH3:23])=[CH:20][CH:21]=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(N(CC)CC)C.Cl>CS(C)=O>[C:22]([C:19]1[O:18][C:17]([S:14]([N:5]2[C:6]([C:7]3[C:8]([F:13])=[N:9][CH:10]=[CH:11][CH:12]=3)=[C:2]([F:1])[C:3]([CH2:25][N:26]([CH3:34])[C:27](=[O:33])[O:28][C:29]([CH3:31])([CH3:30])[CH3:32])=[CH:4]2)(=[O:15])=[O:16])=[CH:21][CH:20]=1)(=[O:24])[CH3:23]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 67397408tert-butyl [(4-fluoro-5-(2-fluoropyridin-3-yl)-1-{[5-(1-hydroxyethyl)-2-furyl]sulfonyl}-1H-pyrrol-3-yl)methyl]methylcarbamate

Product 1

HCID 67396928tert-butyl {[1-[(5-acetyl-2-furyl)sulfonyl]-4-fluoro-5-(2-fluoropyridin-3-yl)-1H-pyrrol-3-yl]methyl}methylcarbamateYield 77.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of tert-butyl [(4-fluoro-5-(2-fluoropyridin-3-yl)-1-{[5-(1-hydroxyethyl)-2-furyl]sulfonyl}-1H-pyrrol-3-yl)methyl]methylcarbamate (234 mg) in dimethyl sulfoxide (3 mL) were added triethylamine (3 mL) and sulfur trioxide pyridine complex (449 mg), and the mixture was stirred at 60° C. for 3 days. 1 mol/L Hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The separated aqueous layer was extracted again with ethyl acetate. The combined organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=9:1→3:2) to give the title compound as a pale-yellow oil (yield 180 mg, 77%).

Workup

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

Sources & evidence

ORD record
ord-e1cbea4c1a8146c6879a2edf9abb6f80
Source dataset
uspto-grants-2015_01
Patent number
US08933105B2

Reaction notes

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