Sodium hydride → tert-butyl {[1-{[5-(1,3-dioxolan-2-yl)-2-furyl]sulfonyl}-4-fluoro-5-(2-fluoropyridin-3-yl)-1H-pyrrol-3-yl]methyl}methylcarbamate

HRID 1426740Notes

Reaction equation

HRID 1426740 reaction equation
[H-].[Na+].[F:3][C:4]1[C:9]([C:10]2[NH:14][CH:13]=[C:12]([CH2:15][N:16]([CH3:24])[C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[C:11]=2[F:25])=[CH:8][CH:7]=[CH:6][N:5]=1.[CH2:26]1OCCOCCOCCOCCOC1.Cl[S:42]([C:45]1[O:49][C:48]([C:50]([O:52][CH3:53])=[O:51])=[CH:47][CH:46]=1)(=[O:44])=[O:43]>O1CCCC1>[O:51]1[CH2:26][CH2:53][O:52][CH:50]1[C:48]1[O:49][C:45]([S:42]([N:14]2[C:10]([C:9]3[C:4]([F:3])=[N:5][CH:6]=[CH:7][CH:8]=3)=[C:11]([F:25])[C:12]([CH2:15][N:16]([CH3:24])[C:17](=[O:23])[O:18][C:19]([CH3:21])([CH3:22])[CH3:20])=[CH:13]2)(=[O:44])=[O:43])=[CH:46][CH:47]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 3633615-Crown-5HCID 2736845Methyl 5-(Chlorosulfonyl)-2-FuroateHCID 67176761tert-butyl {[4-fluoro-5-(2-fluoropyridin-3-yl)-1H-pyrrol-3-yl]methyl}methylcarbamate

Product 1

HCID 67396617tert-butyl {[1-{[5-(1,3-dioxolan-2-yl)-2-furyl]sulfonyl}-4-fluoro-5-(2-fluoropyridin-3-yl)-1H-pyrrol-3-yl]methyl}methylcarbamateYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of sodium hydride (60% in oil, 155 mg) in tetrahydrofuran (10 mL) was added tert-butyl {[5-(2-fluoropyridin-3-yl)-4-fluoro-1H-pyrrol-3-yl]methyl}methylcarbamate (1.04 g) under ice-cooling and the mixture was stirred for 15 min. 15-Crown-5 (354 mg) and a solution of methyl 5-(chlorosulfonyl)-2-furoate in tetrahydrofuran (2 mL) were added dropwise and the mixture was further stirred at room temperature for 1.5 hr. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with water, 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 silica gel column chromatography (eluent: hexane-ethyl acetate=4:1→1:1) to give the title compound as a brown oil (yield 1.33 g, 78%).

Workup

  1. temperaturecooling
  2. stirringthe mixture was further stirred at room temperature for 1.5 hr
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additionthe residue was diluted with water
  5. extractionextracted with ethyl acetate
  6. extractionThe separated aqueous layer was extracted again with ethyl acetate
  7. washThe combined organic layer was washed with saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=4:1→1:1)

Sources & evidence

ORD record
ord-8dae8b4da7794830b0e112701aee1912
Source dataset
uspto-grants-2015_01
Patent number
US08933105B2

Reaction notes

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