Methanol → [1-(2,6-Dichloropyridin-3-yl)cyclopropyl]methanamine

Temperature

-10 °C

To a solution of 1.50 g of 1-(2,6-dichloro-pyridin-3-yl)-cyclopropanecarbonitrile in dry toluene was added slowly at −10° C. 14.8 mL of diisobutylaluminium hydride. The reaction mixture was stirred at −10° C. for 30 min. Subsequently, 1.90 g of sodium borohydride and 20 ml of methanol were added sequentially. The speed of addition was such as to maintain the temperature of the reaction mixture below −5° C. The resulting reaction mixture was stirred at −10° C. for 30 min before being quenched by the addition of 35 ml of a aqueous saturated solution of sodium potassium tartrate and extracted with three portions of diethyl ether. The organic phases were combined, washed with brine, dried over sodium sulphate, filtered and concentrated. 1.66 g of crude material was obtained as yellow oil which was purified by flash chromatography on silica gel with dichloromethane/methanol (95:5) as a solvent. Thus, 367 mg of C-[1-(2,6-dichloro-pyridin-3-yl)-cyclopropyl]-methylamine was obtained as a colorless oil. 1H-NMR (CDCl3): 7.63 ppm (d, 1H), 7.23 ppm (d, 1H), 2.85 ppm (s, 2H), 1.46 (m, 1H), 0.93 ppm (m, 2H), 0.83 ppm (m, 2H).

1. additionThe speed of addition
2. temperatureto maintain the temperature of the reaction mixture below −5° C
3. customThe resulting reaction mixture
4. stirringwas stirred at −10° C. for 30 min
5. custombefore being quenched by the addition of 35 ml of a aqueous saturated solution of sodium potassium tartrate
6. extractionextracted with three portions of diethyl ether
7. washwashed with brine
8. dry with materialdried over sodium sulphate
9. filtrationfiltered
10. concentrationconcentrated
11. custom1.66 g of crude material was obtained as yellow oil which
12. customwas purified by flash chromatography on silica gel with dichloromethane/methanol (95:5) as a solvent

ORD record

ord-03678a4ed8974a3cb65cc0935bd04c75

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09040708B2