1-Iodo-3-methylbutane → 6-(3-Chloro-4-fluoro-phenyl)-8-ethyl-8-methyl-5-(3-methyl-butyl)-5,6,7,8-tetrahydro-[1,5]naphthyridine-2-carboxylic acid methyl ester

HRID 2047704

Reaktionsgleichung

Reaktionsgleichung von HRID 2047704
[CH3:1][O:2][C:3]([C:5]1[CH:14]=[CH:13][C:12]2[NH:11][CH:10]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[C:17]([Cl:22])[CH:16]=3)[CH2:9][C:8]([CH2:24][CH3:25])([CH3:23])[C:7]=2[N:6]=1)=[O:4].[H-].[Na+].I[CH2:29][CH2:30][CH:31]([CH3:33])[CH3:32]>CN(C)C=O>[CH3:1][O:2][C:3]([C:5]1[CH:14]=[CH:13][C:12]2[N:11]([CH2:29][CH2:30][CH:31]([CH3:33])[CH3:32])[CH:10]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[C:17]([Cl:22])[CH:16]=3)[CH2:9][C:8]([CH2:24][CH3:25])([CH3:23])[C:7]=2[N:6]=1)=[O:4]

Komponenten

5

Edukt 3

HCID 109241-Iodo-3-methylbutaneHCID 24758Sodium hydrideHCID 66587522HCID 66587522, Verbindung

Produkt 1

HCID 665877056-(3-Chloro-4-fluoro-phenyl)-8-ethyl-8-methyl-5-(3-methyl-butyl)-5,6,7,8-tetrahydro-[1,5]naphthyridine-2-carboxylic acid methyl esterAusbeute 73,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a 0° C. solution of 6-(3-chloro-4-fluoro-phenyl)-8-ethyl-8-methyl-5,6,7,8-tetrahydro-[1,5]naphthyridine-2-carboxylic acid methyl ester (200 mg, 0.5 mmol) in N,N-dimethylformamide (5 mL) was added a 60% dispersion of sodium hydride in mineral oil (44 mg, 1.1 mmol) portionwise. The mixture was stirred at 0° C. for 30 min and then 1-iodo-3-methyl-butane (327 mg, 1.6 mmol) was added to above mixture dropwise at 0° C. The mixture was stirred at 0° C. for 3 hours and then extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The yellowish residue was purified by ISCO combi-flash chromatography (gradient elution, 0-5% ethyl acetate/hexane) to afford 6-(3-chloro-4-fluoro-phenyl)-8-ethyl-8-methyl-5-(3-methyl-butyl)-5,6,7,8-tetrahydro-[1,5]naphthyridine-2-carboxylic acid methyl ester (160 mg, 67.5%) as a yellow oil. MS (ESI+) [(M+H)+] 433.1.

Aufarbeitung

  1. stirringThe mixture was stirred at 0° C. for 3 hours
  2. extractionextracted with ethyl acetate
  3. washwashed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe yellowish residue was purified by ISCO combi-flash chromatography (gradient elution, 0-5% ethyl acetate/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-94d32a24d5124111b84cf2d5c19ac397
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08592594B2

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