Cesium carbonate → 6-Cyclopropylmethoxy-5-(2-oxo-pyrrolidin-1-yl)-pyridine-2-carboxylic acid

HRID 927451

Reaktionsgleichung

Reaktionsgleichung von HRID 927451
[NH:1]1[CH2:5][CH2:4][CH2:3][C:2]1=[O:6].C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:14]1[CH:15]=[CH:16][C:17]([C:25]([OH:27])=[O:26])=[N:18][C:19]=1[O:20][CH2:21][CH:22]1[CH2:24][CH2:23]1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:22]1([CH2:21][O:20][C:19]2[N:18]=[C:17]([C:25]([OH:27])=[O:26])[CH:16]=[CH:15][C:14]=2[N:1]2[CH2:5][CH2:4][CH2:3][C:2]2=[O:6])[CH2:23][CH2:24]1

Komponenten

6

Edukt 3

HCID 10796Cesium carbonateHCID 120252-PyrrolidoneHCID 710875435-Bromo-6-cyclopropylmethoxy-pyridine-2-carboxylic acid

Produkt 1

HCID 710875066-Cyclopropylmethoxy-5-(2-oxo-pyrrolidin-1-yl)-pyridine-2-carboxylic acidAusbeute 54,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

Under nitrogen atmosphere, pyrrolidin-2-one (375 mg, 4.4 mmol), dimethylbisdiphenyl-phosphinoxanthene (CAS 161265-03-8, 127 mg, 2.4 mmol), tris(dibenzylideneacetone)dipalladium (CAS 51364-51-3, 67 mg, 0.1 mmol) and cesium carbonate (CAS 534-17-8, 1.8 g, 6 mmol) in 1,4-dioxane (100 mL) were added to a solution of 5-bromo-6-cyclopropylmethoxy-pyridine-2-carboxylic acid (Example 9 d, 1 g, 4 mmol) and the reaction mixture was stirred overnight at 110° C. The reaction mixture was concentrated in vacuo, dissolved in water and extracted with ethyl acetate (3×30 mL). The aqueous layer was adjusted to pH=2 with aqueous solution of hydrochloride (1N), the resulting precipitate was collected by filtration and dried. The crude product was purified by column chromatography (silica gel, 20 g, eluting with 30% ethyl acetate in petroleum ether) to give the desired product (600 mg) as a yellow solid; MS (EI): m/e=277.1 [M+H]+.

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutiondissolved in water
  3. extractionextracted with ethyl acetate (3×30 mL)
  4. filtrationthe resulting precipitate was collected by filtration
  5. customdried
  6. customThe crude product was purified by column chromatography (silica gel, 20 g, eluting with 30% ethyl acetate in petroleum ether)

Quellen und Nachweise

ORD-Eintrag
ord-beb942bcc41449dcac63940f122ebd63
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09290451B2

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