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

HRID 869743

Reaction equation

HRID 869743 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.[CH3:41][C:42]1[CH:47]=[CH:46][N:45]=[C:44]([S:48](F)(=[O:50])=[O:49])[CH:43]=1>O1CCCC1.O>[F:3][C:4]1[C:5]([CH2:16][N:17]([CH3:25])[C:18](=[O:24])[O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[CH:6][N:7]([S:48]([C:44]2[CH:43]=[C:42]([CH3:41])[CH:47]=[CH:46][N:45]=2)(=[O:50])=[O:49])[C:8]=1[C:9]1[C:10]([F:15])=[N:11][CH:12]=[CH:13][CH:14]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 3633615-Crown-5HCID 583498404-Methylpyridine-2-sulfonyl fluorideHCID 67176761tert-butyl {[4-fluoro-5-(2-fluoropyridin-3-yl)-1H-pyrrol-3-yl]methyl}methylcarbamate

Product 1

HCID 67178433tert-Butyl ({4-fluoro-5-(2-fluoropyridin-3-yl)-1-[(4-methylpyridin-2-yl)sulfonyl]-1H-pyrrol-3-yl}methyl)methylcarbamateYield 70%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension (3 mL) of sodium hydride (60% in oil, 60 mg) in tetrahydrofuran were added tert-butyl {[4-fluoro-5-(2-fluoropyridin-3-yl)-1H-pyrrol-3-yl]methyl}methylcarbamate (323 mg), 15-crown-5 (330 mg) and 4-methylpyridine-2-sulfonyl fluoride (343 mg) at room temperature, and the mixture was stirred at room temperature for 41 hr. 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=4:1→1:1) to give the title compound as a pale-yellow oil (yield 333 mg, 70%).

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=4:1→1:1)

Sources & evidence

ORD record
ord-ad0c90cd526d41d9b847058b148f2491
Source dataset
uspto-grants-2015_03
Patent number
US08969387B2

Linked notes

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