Sodium hydride → HCID 67395976, compound

HRID 1426745Notes

Reaction equation

HRID 1426745 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.C1OCCOCCOCCOCCOC1.[Cl:41][C:42]1[S:46][C:45]([S:47](Cl)(=[O:49])=[O:48])=[CH:44][CH:43]=1>O1CCCC1.O>[Cl:41][C:42]1[S:46][C:45]([S:47]([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:49])=[O:48])=[CH:44][CH:43]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 3633615-Crown-5HCID 27339255-Chlorothiophene-2-sulfonyl chlorideHCID 67176761tert-butyl {[4-fluoro-5-(2-fluoropyridin-3-yl)-1H-pyrrol-3-yl]methyl}methylcarbamate

Product 1

HCID 67395976HCID 67395976, compoundYield 98%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of sodium hydride (60% in oil, 24.0 mg) in tetrahydrofuran (2 mL) was added tert-butyl {[5-(2-fluoropyridin-3-yl)-4-fluoro-1H-pyrrol-3-yl]methyl}methylcarbamate (150 mg) under ice-cooling, and the mixture was stirred for 15 min. 15-Crown-5 (133 mg) and a solution of 5-chlorothiophene-2-sulfonyl chloride in tetrahydrofuran (1 mL) were added dropwise and the mixture was further stirred at room temperature for 1 hr. The reaction mixture 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=9:1→2:1) to give the title compound as a colorless oil (yield 229 mg, 98%).

Workup

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

Sources & evidence

ORD record
ord-82dfb158f5da4cc2976f4b9e6cbc003e
Source dataset
uspto-grants-2015_01
Patent number
US08933105B2

Reaction notes

Loading…