4-Hydroxymethylpyridine → N-(2,4-dimethylphenyl)-N-isobutyl-4-((pyridine-4-ylmethoxy)methyl)benzenesulfonamide

HRID 1746408Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1746408
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:18]=2[CH3:24])[CH2:13][CH:14]([CH3:16])[CH3:15])(=[O:11])=[O:10])=[CH:5][CH:4]=1.[N:25]1[CH:30]=[CH:29][C:28]([CH2:31][OH:32])=[CH:27][CH:26]=1.[H-].[Na+]>CC1CCCO1.CS(C)=O.ClCCl.O.CO>[CH3:24][C:18]1[CH:19]=[C:20]([CH3:23])[CH:21]=[CH:22][C:17]=1[N:12]([CH2:13][CH:14]([CH3:16])[CH3:15])[S:9]([C:6]1[CH:5]=[CH:4][C:3]([CH2:2][O:32][CH2:31][C:28]2[CH:29]=[CH:30][N:25]=[CH:26][CH:27]=2)=[CH:8][CH:7]=1)(=[O:11])=[O:10]

Komponenten

9

Edukt 3

HCID 114724-HydroxymethylpyridineHCID 24758Sodium hydrideHCID 867315854-(bromomethyl)-N-(2,4-dimethylphenyl)-N-isobutylbenzenesulfonamide

Produkt 1

HCID 71543593N-(2,4-dimethylphenyl)-N-isobutyl-4-((pyridine-4-ylmethoxy)methyl)benzenesulfonamideAusbeute 9 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 679Dimethyl SulfoxideLösungsmittelHCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 73012-MethyltetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

To a solution of crude 4-(bromomethyl)-N-(2,4-dimethylphenyl)-N-isobutylbenzenesulfonamide (100 mg, 0.122 mmol) and pyridine-4-ylmethanol (13.30 mg, 0.122 mmol) in 2-Methyltetrahydrofuran (2-MeTHF) (1 mL) and dimethyl sulfoxide (DMSO) (0.5 mL) stirred in air at RT was added solid sodium hydride (4.87 mg, 0.122 mmol) in one charge, tip of spatula. The reaction mixture was stirred at 20° C. for 16 hours. Reaction was carefully quenched with methanol (0.5 mL) and water (0.5 mL) and evaporated in vacuo to give a residue in DMSO. This was diluted with dichloromethane (10 mL) and water (10 mL) and stirred vigorously for 10 min. The layers were separated by hydrophobic frit and the organic fraction evaporated to give the crude product. The samples were dissolved in 1:1 MeOH:DMSO 1 mL and purified by mass directed autoprep on Sunfire C18 column using acetonitrile:water with a formic acid modifier. The solvent was dried under a stream of nitrogen in the Radleys blowdown apparatus to give the required product N-(2,4-dimethylphenyl)-N-isobutyl-4-((pyridine-4-ylmethoxy)methyl)benzenesulfonamide (4.8 mg, 10.94 μmol, 8.98% yield)

Aufarbeitung

  1. additioncharge
  2. customReaction
  3. customwas carefully quenched with methanol (0.5 mL) and water (0.5 mL)
  4. customevaporated in vacuo
  5. customto give a residue in DMSO
  6. stirringstirred vigorously for 10 min
  7. customThe layers were separated by hydrophobic frit
  8. customthe organic fraction evaporated
  9. customto give the crude product
  10. customDMSO 1 mL and purified by mass
  11. customThe solvent was dried under a stream of nitrogen in the Radleys blowdown apparatus

Quellen und Nachweise

ORD-Eintrag
ord-0673965fd8a04499b87c3ea79fc48af6
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09150508B2

Notizen zur Reaktion

Wird geladen…