Sodium hydride → HCID 67395940, compound

HRID 1426748Notes

Reaction equation

HRID 1426748 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[CH:49]=[CH:48][S:47][C:46]=1[C:50]([O:52][CH3:53])=[O:51])(=[O:44])=[O:43]>O1CCCC1>[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[CH:49]=[CH:48][S:47][C:46]=2[C:50]([O:52][CH3:53])=[O:51])(=[O:43])=[O:44])[CH:13]=1)[CH3:24])=[O:23])([CH3:21])([CH3:22])[CH3:20]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 3633615-Crown-5HCID 27367332-Thiophenecarboxylic acid, 3-(chlorosulfonyl)-, methyl esterHCID 67176761tert-butyl {[4-fluoro-5-(2-fluoropyridin-3-yl)-1H-pyrrol-3-yl]methyl}methylcarbamate

Product 1

HCID 67395940HCID 67395940, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of sodium hydride (60% in oil, 14.8 mg) in tetrahydrofuran (3 mL) was added tert-butyl {[5-(2-fluoropyridin-3-yl)-4-fluoro-1H-pyrrol-3-yl]methyl}methylcarbamate (100 mg) under ice-cooling, and the mixture was stirred for 5 min. 15-Crown-5 (81.7 mg) and methyl 3-(chlorosulfonyl)thiophene-2-carboxylate were added dropwise and the mixture was further stirred under ice-cooling for 2 hr. The reaction mixture was concentrated under reduced pressure, 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 158 mg, 97%).

Workup

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

Sources & evidence

ORD record
ord-935b87abac054fcdb6b322bdfb4782a4
Source dataset
uspto-grants-2015_01
Patent number
US08933105B2

Reaction notes

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