Sodium hydride → Methyl 5-((6-methoxy-2-(4-methoxyphenyl)-1-oxidobenzo[b]thiophen-3-yl)oxy)picolinate

HRID 332884Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 332884
[OH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([O:10][CH3:11])=[O:9])=[N:6][CH:7]=1.[H-].[Na+].Br[C:15]1[C:19]2[CH:20]=[CH:21][C:22]([O:24][CH3:25])=[CH:23][C:18]=2[S:17](=[O:26])[C:16]=1[C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=1>CN(C=O)C>[CH3:25][O:24][C:22]1[CH:21]=[CH:20][C:19]2[C:15]([O:1][C:2]3[CH:3]=[CH:4][C:5]([C:8]([O:10][CH3:11])=[O:9])=[N:6][CH:7]=3)=[C:16]([C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)[S:17](=[O:26])[C:18]=2[CH:23]=1

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 4715126Methyl 5-hydroxypyridine-2-carboxylateHCID 159594683-Bromo-6-methoxy-2-(4-methoxyphenyl)benzothiophene 1-oxide

Produkt 1

HCID 86730670Methyl 5-((6-methoxy-2-(4-methoxyphenyl)-1-oxidobenzo[b]thiophen-3-yl)oxy)picolinateAusbeute 52,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of methyl 5-hydroxypyridine-2-carboxylate (0.273 g, 1.78 mmol) in DMF (6.84 mL) at room temperature was added sodium hydride (60% suspension in oil, 0.043 g, 1.78 mmol) and the resulting mixture was stirred at room temperature for 30 mins. After 30 min at room temperature 3-bromo-6-methoxy-2-(4-methoxyphenyl)benzothiophene 1-oxide (0.5 g, 1.37 mmol) was added and the reaction was heated to 80° C. for 18 h. Upon completion the reaction was cooled to room temperature, quenched with water and extracted with DCM. The organic layers were combined, passed through a phase separator and concentrated in vacuo to give the crude product, which was purified by column chromatography (SiO2, 0-75% EtOAc/heptane) to afford methyl 5-((6-methoxy-2-(4-methoxyphenyl)-1-oxidobenzo[b]thiophen-3-yl)oxy)picolinate (314 mg, 0.72 mmol, 52% yield). 1H NMR (400 MHz, CDCl3) δ ppm=3.73 (s, 3H), 3.84 (s, 3H), 3.90-3.92 (m, 3H), 6.79-6.86 (m, 2H), 6.91 (dd, J=8.59, 2.53 Hz, 1H), 7.03 (d, J=8.59 Hz, 1H), 7.30 (dd, J=8.59, 3.03 Hz, 1H), 7.48 (d, J=2.53 Hz, 1H), 7.55-7.60 (m, 2H), 7.95 (d, J=8.59 Hz, 1H), 8.55 (d, J=2.02 Hz, 1H). LC/MS (m/z, MH+): 438.2.

Aufarbeitung

  1. temperaturethe reaction was heated to 80° C. for 18 h
  2. temperatureUpon completion the reaction was cooled to room temperature
  3. customquenched with water
  4. extractionextracted with DCM
  5. concentrationconcentrated in vacuo
  6. customto give the crude product, which
  7. customwas purified by column chromatography (SiO2, 0-75% EtOAc/heptane)

Quellen und Nachweise

ORD-Eintrag
ord-407dc81d84c94f6097678c56f4029eaf
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08877801B2

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