Sodium hydride → tert-butyl{1-[2-(7-fluoro-2-oxoquinoxalin-1(2H)-yl)ethyl]piperidin-4-yl}carbamate

HRID 1644431

Reaktionsgleichung

Reaktionsgleichung von HRID 1644431
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([N:6]=[CH:7][C:8](=[O:12])[NH:9]2)=[CH:4][CH:3]=1.FC1C=C2C(=CC=1)NC(=O)C=N2.[H-].[Na+].CS(O[CH2:32][CH2:33][N:34]1[CH2:39][CH2:38][CH:37]([NH:40][C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:36][CH2:35]1)(=O)=O>CN(C=O)C.O.C(OCC)C>[C:44]([O:43][C:41](=[O:42])[NH:40][CH:37]1[CH2:38][CH2:39][N:34]([CH2:33][CH2:32][N:9]2[C:10]3[C:5](=[CH:4][CH:3]=[C:2]([F:1])[CH:11]=3)[N:6]=[CH:7][C:8]2=[O:12])[CH2:35][CH2:36]1)([CH3:47])([CH3:46])[CH3:45]

Komponenten

8

Edukt 4

HCID 24758Sodium hydrideHCID 126863866-Fluoro-1,2-dihydroquinoxalin-2-one2×HCID 217275347-fluoroquinoxalin-2(1H)-one2×HCID 568344782-(4-((Tert-butoxycarbonyl)amino)piperidin-1-yl)ethyl methanesulfonate2×

Produkt 1

HCID 59397942tert-butyl{1-[2-(7-fluoro-2-oxoquinoxalin-1(2H)-yl)ethyl]piperidin-4-yl}carbamate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 3283Diethyl EtherLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A suspension of a 1:1 mixture of 7-fluoroquinoxalin-2(1H)-one (Intermediate 143) and 6-fluoroquinoxalin-2(1H)-one (Intermediate 144) (1.5 g total, 9.1 mmol) was treated with sodium hydride (60% in oil, 0.44 g, 11.0 mmol) at 0° C. The reaction was allowed to stir at room temperature for 2 hours. The reaction mixture was cooled to 0° C. and 2-{4-[(tert-butoxycarbonyl)amino]piperidin-1-yl}ethyl methanesulfonate (Intermediate 6, 1.33 mmol/mL, 11.0 mmol), dissolved in dry DMF (5 mL) was added and it was stirred at room temperature overnight. The reaction mixture was diluted with water and with diethyl ether (5×50 mL). The combined organic phases were dried over sodium sulfate and concentrated to dryness under reduced pressure. Chromatography with hexanes/acetone (5:1 to 3:1). The higher Rf material was isolated as a mixture of Intermediate 141 with an O-alkylated isomer, which was rechromatographed on silica gel with hexanes/ethyl acetate (1:3) to give pure Intermediate 141 as a colorless solid, 0.24 g, 14%. Isolation of the lower Rf material from the first column gave 0.38 g (21%) of pure Intermediate 142 as a colorless solid.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. additionwas added
  3. stirringit was stirred at room temperature overnight
  4. dry with materialThe combined organic phases were dried over sodium sulfate
  5. concentrationconcentrated to dryness under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-4b4db1d1fffe40f284a1400c2f0eaae3
Quelldatensatz
uspto-grants-2012_02
Patentnummer
US08124602B2

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