Reaktion #168097

Reaktionsgleichung

[(1-Ethoxy-cyclopropyl)oxy]trimethylsilane

1-(5-bromopyridin-2-yl)-piperazine

Water

NaCNBH3

→

1-(5-Bromopyridin-2-yl)-4-cyclopropylpiperazine

Lösungsmittel

THF

THF

acetic acid

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwas then heated
2. 2
   Temperaturat reflux temperature for 3 hours
3. 3
   Sonstigeevaporated to dryness in vacuo
4. 4
   workup.DISSOLUTIONThe residue was dissolved in a mixture of dichloromethane (200 mL) and water (50 mL) and 4 N sodium hydroxide (20 mL)
5. 5
   workup.ADDITIONwas added to pH 8-9
6. 6
   SonstigeThe organic phase was isolated
7. 7
   Extraktionthe aqeoues phase was extracted with further dichloromethane (100 mL)
8. 8
   SonstigeThe combined organic phases were evaporated to dryness in vacuo
9. 9
   Sonstigethe residue was purified on a silica gel column (gradient: from 5% ethyl acetate in heptane to 100% ethyl acetate over 40 min.)

Vorschrift

[(1-Ethoxy-cyclopropyl)oxy]trimethylsilane (26 mL, 129.3 mmol) was added to a solution of 1-(5-bromopyridin-2-yl)-piperazine (15 g, 62.0 mmol) in THF (120 mL). Water (24 mL), acetic acid (11 mL), and 1 M NaCNBH3 in THF (90 mL, 90 mmol) were added to the reaction mixture, which was then heated at reflux temperature for 3 hours. The resulting solution was cooled to rt and evaporated to dryness in vacuo. The residue was dissolved in a mixture of dichloromethane (200 mL) and water (50 mL) and 4 N sodium hydroxide (20 mL) was added to pH 8-9. The organic phase was isolated and the aqeoues phase was extracted with further dichloromethane (100 mL). The combined organic phases were evaporated to dryness in vacuo and the residue was purified on a silica gel column (gradient: from 5% ethyl acetate in heptane to 100% ethyl acetate over 40 min.). This afforded 13.1 g (75%) of 1-(5-bromopyridin-2-yl)-4-cyclopropylpiperazine.

Quelle