Reaktion #309844

Reaktionsgleichung

Sodium hydride

7-hydroxy-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid tert-butyl ester

methyl 5-chloro-2-pyrazinecarboxylate

→

title compound

Ausbeute 58.5%

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

Ausbeute 58.5%

Lösungsmittel

dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturto warm to room temperature
2. 2
   TemperaturThe mixture was cooled in an ice-water bath
3. 3
   Temperaturto warm to room temperature
4. 4
   workup.STIRRINGstirred for 18 hours
5. 5
   FiltrationThe resulting solid was collected by filtration
6. 6
   Waschenwashed with water
7. 7
   workup.DISSOLUTIONdissolved in ethyl acetate (1500 ml)
8. 8
   WaschenThe ethyl acetate layer was washed with brine (200 ml)
9. 9
   Sonstigedried under sodium sulfate
10. 10
    Sonstigeevaporated in vacuo
11. 11
    SonstigeThe crude product was purified by column chromatography
12. 12
    Wascheneluting with a mixture of ethyl acetate:hexane (1:2)

Vorschrift

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).

Quelle