Sodium hydride → Methyl 5-{[4-{[(tert-butoxycarbonyl)(methyl)amino]methyl}-3-fluoro-2-(2-fluoropyridin-3-yl)-1H-pyrrol-1-yl]sulfonyl}-2-furoate

HRID 1426735Notes

Reaction equation

HRID 1426735 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[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>[C:19]([O:18][C:17]([N:16]([CH2:15][C:12]1[C:11]([F:25])=[C:10]([C:9]2[C:4]([F:3])=[N:5][CH:6]=[CH:7][CH:8]=2)[N:14]([S:42]([C:45]2[O:49][C:48]([C:50]([O:52][CH3:53])=[O:51])=[CH:47][CH:46]=2)(=[O:43])=[O:44])[CH:13]=1)[CH3:24])=[O:23])([CH3:21])([CH3:22])[CH3:20]

Participants

7

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 67395998Methyl 5-{[4-{[(tert-butoxycarbonyl)(methyl)amino]methyl}-3-fluoro-2-(2-fluoropyridin-3-yl)-1H-pyrrol-1-yl]sulfonyl}-2-furoateYield 83%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of sodium hydride (60% in oil, 64.3 mg) in tetrahydrofuran (2 mL) was added a solution of tert-butyl {[5-(2-fluoropyridin-3-yl)-4-fluoro-1H-pyrrol-3-yl]methyl}methylcarbamate (400 mg) in tetrahydrofuran (1 mL) at room temperature and the mixture was stirred for 15 min. 15-Crown-5 (354 mg) and methyl 5-(chlorosulfonyl)-2-furoate were added dropwise and the mixture was further stirred at room temperature for 30 min. 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=6:1→2:1) to give the title compound as a pale-yellow oil (yield 522 mg, 83%).

Workup

  1. stirringthe mixture was further stirred at room temperature for 30 min
  2. extractionextracted with ethyl acetate
  3. extractionThe separated aqueous layer was extracted again with ethyl acetate
  4. washThe combined organic layer 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=6:1→2:1)

Sources & evidence

ORD record
ord-c7cf809f6ead461e9f2534a6112849e0
Source dataset
uspto-grants-2015_01
Patent number
US08933105B2

Reaction notes

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