Boron trifluoride etherate → 1-(5-Bromopyridin-2-yl)cyclopropan-1-amine

Participants

Reaction Conditions

Reaction Steps

5-bromopicolinonitrile (D9) (43.6 g, 0.238 mol) was suspended in diethyl ether (1.3 L) and the resulting mixture was cooled to −78° C. Titanium (IV) isopropoxide (74.4 g, 0.262 mol) was added dropwise and the reaction mixture was stirred for 5 min. Ethylmagnesium bromide 1M in diethyl ether (525 ml, 0.525 mol) was added dropwise and the resulting reaction mixture was stirred for 30 mins at −78° C. The reaction mixture was allowed to warm to room temperature for 1 hour then boron trifluoride etherate (107 ml) was added dropwise. After stirred at room temperature for 2 hours, the reaction was quenched with 1M HCl (1.5 L). The aqueous layer was washed with diethyl ether (1 L) and then basified (pH=9) with 2N NaOH (1.25 L). The resulting mixture was extracted with ethyl acetate. The organic layer was dried over Na2SO4 and evaporated in vacuo. The residue was purified by column chromatography eluting with a mixture petroleum ether/ethyl acetate 1:1. Collected fractions after solvent evaporation afforded the title compound (D10) (15.7 g) as a grey solid.

Provenance & Evidence