Sodium hydride → 4-chloro-5-(2-fluoropyridin-3-yl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehyde

HRID 2090751Notes

Reaction equation

HRID 2090751 reaction equation
[Cl:1][C:2]1[C:3]([CH:14]=[O:15])=[CH:4][NH:5][C:6]=1[C:7]1[C:8]([F:13])=[N:9][CH:10]=[CH:11][CH:12]=1.[H-].[Na+].C1OCCOCCOCCOCCOC1.[N:33]1[CH:38]=[CH:37][CH:36]=[C:35]([S:39](Cl)(=[O:41])=[O:40])[CH:34]=1>O1CCCC1.[Cl-].[Na+].O>[Cl:1][C:2]1[C:3]([CH:14]=[O:15])=[CH:4][N:5]([S:39]([C:35]2[CH:34]=[N:33][CH:38]=[CH:37][CH:36]=2)(=[O:41])=[O:40])[C:6]=1[C:7]1[C:8]([F:13])=[N:9][CH:10]=[CH:11][CH:12]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 3633615-Crown-5HCID 3164136Pyridine-3-sulfonyl chlorideHCID 866239794-chloro-5-(2-fluoropyridin-3-yl)-1H-pyrrole-3-carbaldehyde

Product 1

HCID 866310044-chloro-5-(2-fluoropyridin-3-yl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrole-3-carbaldehydeYield 81.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution (20 mL) of 4-chloro-5-(2-fluoropyridin-3-yl)-1H-pyrrole-3-carbaldehyde (270 mg) in tetrahydrofuran was added sodium hydride (60% in oil, 100 mg) at room temperature and the mixture was stirred for 30 min. 15-Crown-5 (530 mg) was added dropwise and the mixture was stirred for 30 min. 3-Pyridylsulfonyl chloride (321 mg) was added, and the mixture was further stirred for 1 hr. The reaction mixture was diluted with saturated brine, and the mixture was extracted with ethyl acetate. The extract 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=1:1→1:4), and crystallized from diethyl ether to give the title compound as colorless crystals (yield 358 mg, 81%).

Workup

  1. stirringthe mixture was stirred for 30 min
  2. stirringthe mixture was further stirred for 1 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=1:1→1:4)
  8. customcrystallized from diethyl ether

Sources & evidence

ORD record
ord-c8c20c54014446c78bbfb9e883c1386f
Source dataset
uspto-grants-2013_05
Patent number
US08436187B2

Reaction notes

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