Sodium hydride → 1,1-Dimethylethyl 7-({5-[(methyloxy)carbonyl]-2-pyrazinyl}oxy)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate

HRID 641462Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 641462
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:16][CH2:15][C:14]2[CH:17]=[C:18]([OH:21])[CH:19]=[CH:20][C:13]=2[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Cl[C:23]1[N:24]=[CH:25][C:26]([C:29]([O:31][CH3:32])=[O:30])=[N:27][CH:28]=1>CN(C)C=O>[CH3:32][O:31][C:29]([C:26]1[N:27]=[CH:28][C:23]([O:21][C:18]2[CH:19]=[CH:20][C:13]3[CH2:12][CH2:11][N:10]([C:8]([O:7][C:3]([CH3:6])([CH3:4])[CH3:5])=[O:9])[CH2:16][CH2:15][C:14]=3[CH:17]=2)=[N:24][CH:25]=1)=[O:30]

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 406081Methyl 5-chloropyrazine-2-carboxylateHCID 18173274tert-butyl 7-hydroxy-2,3,4,5-tetrahydro-1H-3-benzazepine-3-carboxylate

Produkt 1

HCID 589845771,1-Dimethylethyl 7-({5-[(methyloxy)carbonyl]-2-pyrazinyl}oxy)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylateAusbeute 58,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
5 °C

Versuchsvorschrift

Sodium hydride (60% dispersion in mineral oil) (6.4 g, 0.16 mol) was added portionwise to a solution of 7-hydroxy-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid tert-butyl ester (PCT Int. Appl. (2002), WO 02/40471) (40 g, 0.15 mol) in dry dimethylformamide (200 ml) cooled to 5° C. over 15 minutes. After 15 minutes, the mixture was allowed to warm to room temperature and stirred for 60 minutes. The mixture was cooled in an ice-water bath and methyl 5-chloro-2-pyrazinecarboxylate (31.2 g, 0.18 mol) was added portionwise. The mixture was allowed to warm to room temperature and stirred for 18 hours. The mixture was poured onto water (500 ml) and ice (500 ml) and stirred until the ice had melted. The resulting solid was collected by filtration, washed with water and dissolved in ethyl acetate (1500 ml). The ethyl acetate layer was washed with brine (200 ml), dried under sodium sulfate and evaporated in vacuo. The crude product was purified by column chromatography eluting with a mixture of ethyl acetate:hexane (1:2) to afford the title compound (35.07 g).

Aufarbeitung

  1. temperatureto warm to room temperature
  2. temperatureThe mixture was cooled in an ice-water bath
  3. temperatureto warm to room temperature
  4. stirringstirred for 18 hours
  5. filtrationThe resulting solid was collected by filtration
  6. washwashed with water
  7. dissolutiondissolved in ethyl acetate (1500 ml)
  8. washThe ethyl acetate layer was washed with brine (200 ml)
  9. customdried under sodium sulfate
  10. customevaporated in vacuo
  11. customThe crude product was purified by column chromatography
  12. washeluting with a mixture of ethyl acetate:hexane (1:2)

Quellen und Nachweise

ORD-Eintrag
ord-5744df05e13e4953bfd896cd14ba70d7
Quelldatensatz
uspto-grants-2010_04
Patentnummer
US07696193B2

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