Oxalyl chloride → Mk-0736

HRID 22861Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 22861
[CH2:1]([S:3]([CH2:6][CH2:7][CH2:8][C:9]12[CH2:16][CH2:15][C:12]([C:17]([NH:19][CH3:20])=O)([CH2:13][CH2:14]1)[CH2:11][CH2:10]2)(=[O:5])=[O:4])[CH3:2].C(Cl)(=O)C(Cl)=O.[F:27][C:28]([F:41])([F:40])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[C:35]1NN=[N:37][N:36]=1>C(Cl)Cl.CN(C=O)C>[CH2:1]([S:3]([CH2:6][CH2:7][CH2:8][C:9]12[CH2:16][CH2:15][C:12]([C:17]3[N:19]([CH3:20])[C:35]([C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=4[C:28]([F:27])([F:41])[F:40])=[N:36][N:37]=3)([CH2:13][CH2:14]1)[CH2:11][CH2:10]2)(=[O:5])=[O:4])[CH3:2]

Komponenten

6

Edukt 3

HCID 65578Oxalyl chlorideHCID 207550394-[3-(ethylsulfonyl)propyl]-N-methylbicyclo[2.2.2]octane-1-carboxamideHCID 178506136HCID 178506136, Verbindung

Produkt 1

HCID 22591684Mk-0736

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideKatalysatorHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

Methyl amide 11-9 (0.470 g, 1.56 mmol) was dissolved in anhydrous methylene chloride (5 mL) and treated with oxalyl chloride (2M in methylene chloride, 1.56 mL, 3.12 mmol) and DMF (2 drops). The solution was stirred at room temperature for 1 h, then solvent removed by evaporation under reduced pressure. The residue was redissolved in anhydrous toluene (7 mL) and treated with 5[2-(trifluoromethyl)phenyl]1H-tetrazole (368 mg, 1.72 mmol). The mixture was refluxed for 18 h. The reaction was cooled to room temperature and the precipitate was filtered and washed to give 300 mg of crude product as the HCl salt. The salt was taken up in methylene chloride/1N HCl and the aqueous layer was washed with two additional portions of methylene chloride. The organic layers were combined and evaporated and the residue was chromatographed by flash silica gel chromatography. Elution was carried out with a gradient ranging from 0 to 5% methanol/methylene chloride. The appropriate fractions were combined and evaporated to give 3-{4-[3-(ethylsulfonyl)propyl]bicyclo[2.2.2]oct-1-yl}-4methyl-5-[2-(trifluoromethyl)phenyl]-4H -1,2,4-triazole (11-10) as a white powder.

Aufarbeitung

  1. customsolvent removed by evaporation under reduced pressure
  2. dissolutionThe residue was redissolved in anhydrous toluene (7 mL)
  3. temperatureThe mixture was refluxed for 18 h
  4. temperatureThe reaction was cooled to room temperature
  5. filtrationthe precipitate was filtered
  6. washwashed
  7. customto give 300 mg of crude product as the HCl salt
  8. washthe aqueous layer was washed with two additional portions of methylene chloride
  9. customevaporated
  10. customthe residue was chromatographed by flash silica gel chromatography
  11. washElution
  12. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-f545b4c0fbe840348f00d557d52632f0
Quelldatensatz
uspto-grants-2005_02
Patentnummer
US06849636B2

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