Reaktion #965642

Reaktionsgleichung

diisobutylaluminium hydride

1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropanecarbonitrile

diisobutylaluminium hydride

potassium sodium tartrate

→

C-[1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropyl]-methylamine

Ausbeute 46.4%

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe reaction mixture was warmed to 40° C.
2. 2
   workup.STIRRINGthe resulting mixture was stirred for 1 hour
3. 3
   ExtraktionThe aqueous phase was extracted with three 25 ml portions dichloromethane
4. 4
   TrocknenThe organic phase was dried over sodium sulfate
5. 5
   Filtrationfiltered
6. 6
   Einengenconcentrated
7. 7
   Sonstige140 mg of crude material was obtained as a yellow sticky solid
8. 8
   SonstigeThe residue was partitioned between 1N aqueous hydrochloric acid and ethyl acetate
9. 9
   workup.ADDITIONThe aqueous phase was adjusted to pH 14 by addition of an aqueous solution of sodium hydroxide
10. 10
    Extraktionextracted with ethyl acetate
11. 11
    TrocknenThe organic phase was dried over sodium sulfate
12. 12
    Filtrationfiltered
13. 13
    Einengenconcentrated

Vorschrift

106 mg of 1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropanecarbonitrile (step 2) was dissolved in 2 ml of dichloromethane and was cooled down to −78° C. Then 0.91 ml of diisobutylaluminium hydride (1 M in tetrahydrofuran) was added dropwise. The reaction mixture was stirred at −78° C. for 1h, then at ambient temperature for three days. Then 0.40 ml of diisobutylaluminium hydride solution was added again at −78° C. and the reaction mixture was warmed to 40° C. and stirred for 24 hours. The reaction mixture was poured into a saturated solution of potassium sodium tartrate and the resulting mixture was stirred for 1 hour. The aqueous phase was extracted with three 25 ml portions dichloromethane. The organic phase was dried over sodium sulfate, filtered and concentrated. 140 mg of crude material was obtained as a yellow sticky solid. The residue was partitioned between 1N aqueous hydrochloric acid and ethyl acetate. The aqueous phase was adjusted to pH 14 by addition of an aqueous solution of sodium hydroxide and extracted with ethyl acetate. The organic phase was dried over sodium sulfate, filtered and concentrated. Thus, 50 mg of C-[1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropyl]-methylamine was obtained as a yellow sticky solid. 1H-NMR (CDCl3): 8.50 ppm (s, 1H), 7.83 ppm (s, 1H), 2.95 ppm (s, 2H), 1.40 ppm (s, 2H, broad), 0.99 ppm (m, 2H), 0.90 ppm (m, 2H).

Quelle