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

HRID 880861Notes

Reaction equation

HRID 880861 reaction equation
[H-].[Na+].[F:3][C:4]1[C:5]([CH2:16][N:17]([CH3:25])[C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:6][NH:7][C:8]=1[C:9]1[C:10]([F:15])=[N:11][CH:12]=[CH:13][CH:14]=1.C1OCCOCCOCCOCCOC1.[Cl:41][C:42]1[CH:43]=[C:44]([S:48](Cl)(=[O:50])=[O:49])[CH:45]=[N:46][CH:47]=1>O1CCCC1.O>[Cl:41][C:42]1[CH:43]=[C:44]([S:48]([N:7]2[C:8]([C:9]3[C:10]([F:15])=[N:11][CH:12]=[CH:13][CH:14]=3)=[C:4]([F:3])[C:5]([CH2:16][N:17]([CH3:25])[C:18](=[O:24])[O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[CH:6]2)(=[O:50])=[O:49])[CH:45]=[N:46][CH:47]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 3633615-Crown-5HCID 545947055-Chloropyridine-3-sulfonyl chlorideHCID 67176761tert-butyl {[4-fluoro-5-(2-fluoropyridin-3-yl)-1H-pyrrol-3-yl]methyl}methylcarbamate

Product 1

HCID 67176466tert-Butyl ({1-[(5-chloropyridin-3-yl)sulfonyl]-4-fluoro-5-(2-fluoropyridin-3-yl)-1H-pyrrol-3-yl}methyl)methylcarbamateYield 78.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of sodium hydride (60% in oil, 52 mg) in tetrahydrofuran (3 mL) were added tert-butyl {[4-fluoro-5-(2-fluoropyridin-3-yl)-1H-pyrrol-3-yl]methyl}methylcarbamate (323 mg), 15-crown-5 (286 mg) and a solution of 5-chloropyridine-3-sulfonyl chloride (318 mg) in tetrahydrofuran (2 mL) at room temperature, and the mixture was stirred for 20 min. The reaction mixture was diluted with water and extracted with ethyl acetate. The separated aqueous layer was extracted again with ethyl acetate. Combined organic layers were 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=9:17:3) to give the title compound as a colorless oil (yield 391 mg, 78%).

Workup

  1. extractionextracted with ethyl acetate
  2. extractionThe separated aqueous layer was extracted again with ethyl acetate
  3. washCombined organic layers were washed with 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=9:17:3)

Sources & evidence

ORD record
ord-6c6dbd4162c94403aa3982fb10a55c2f
Source dataset
uspto-grants-2015_03
Patent number
US08993598B2

Reaction notes

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