Cesium carbonate → (7-((3,4-Difluorobenzyl)oxy)-1,5-naphthyridin-3-yl)methanol

HRID 1748411Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1748411
[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][C:24]=1[F:25])[CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([C:17](OCC)=[O:18])[CH:13]=[N:14]2)=[N:9][CH:8]=1.OC1C=C2C(C=C(C(OCC)=O)C=N2)=NC=1.C([O-])([O-])=O.[Cs+].[Cs+].FC1C=C(C=CC=1F)CBr>CN(C=O)C.O.CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][C:24]=1[F:25])[CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12]([CH2:17][OH:18])[CH:13]=[N:14]2)=[N:9][CH:8]=1

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 5814364-(Bromomethyl)-1,2-difluorobenzeneHCID 90417578Ethyl 7-((3,4-difluorobenzyl)oxy)-1,5-naphthyridine-3-carboxylateHCID 136227102Ethyl 7-hydroxy-1,5-naphthyridine-3-carboxylate2×

Produkt 1

HCID 86301659(7-((3,4-Difluorobenzyl)oxy)-1,5-naphthyridin-3-yl)methanolAusbeute 64 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Ethyl 7-((3,4-difluorobenzyl)oxy)-1,5-naphthyridine-3-carboxylate. To a solution of ethyl 7-hydroxy-1,5-naphthyridine-3-carboxylate (Intermediate 4, 1.0 g, 4.5 mmol) in DMF (20 mL) was added Cs2CO3 (2.2 g, 6.75 mmol), followed by 3,4-difluorobenzyl bromide (0.682 mL, 5.02 mmol). The reaction was stirred at ambient temperature for 72 h. The crude reaction mixture was poured into EtOAc and water. The aqueous layer was extracted with EtOAc and the combined organic fractions were washed with brine and concentrated under reduced pressure onto silica. Purification (FCC, SiO2, 0-60%, EtOAc/hexanes) afforded the title compound as a white solid (1.05 g, 64%) 1H NMR (400 MHz, CDCl3) δ 9.48-9.41 (m, 1H), 8.97 (s, 1H), 8.89-8.82 (m, 1H), 7.69 (s, 1H), 7.37-7.29 (m, 1H), 7.25-7.19 (m, 2H), 5.20 (s, 2H), 4.54-4.40 (m, 2H), 1.51-1.41 (m, 3H). [M+H]=345.2.

Aufarbeitung

  1. customThe crude reaction mixture
  2. extractionThe aqueous layer was extracted with EtOAc
  3. washthe combined organic fractions were washed with brine
  4. concentrationconcentrated under reduced pressure onto silica
  5. customPurification (FCC, SiO2, 0-60%, EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-5fb1c5c2626c42a6959f71623019e531
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09150572B2

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