Hydrochloric Acid → 1-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclopropan-1-amine

Participants

Reaction Conditions

Reaction Steps

In a 40 mL reaction tube was added 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (500 mg, 2.18 mmol) and titanium(IV) isopropoxide (710 μl, 2.40 mmol) in anhydrous tetrahydrofuran (11 ml) to give a colourless solution. The reaction mixture was cooled to −70° C. under a nitrogen atmosphere, followed by the dropwise addition of ethylmagnesium bromide (1M in THF, 4.80 ml, 4.80 mmol) over a period of 30 minutes. The resulting orange solution was stirred at −78° C. for 10 minutes, followed by warming to room temperature and stirring for 60 minutes. After this period, boron trifluoride diethyl etherate (540 μl, 4.37 mmol) was added and the mixture stirred at room temperature for 60 minutes. To the reaction was then added 1M HCl solution (6 ml) and stirred for 15 minutes before basification with 2M NaOH solution. The organic phase was separated and the aqueous washed with ethyl acetate (3×4 mL). The combined organic phases were dried over Na2SO4, filtered and concentrated to dryness under reduced pressure. The residue was purified by Biotage chromatography (cyclohexane:ethyl acetate, gradient elution from 90:10 to 0:100) to give the desired product as an off-white solid (70 mg, 12% yield). 1H-NMR (500 MHz, CDCl3) δ 7.76 (2H, d), 7.29 (2H, d), 2.32 (2H, br s), 1.34 (12H, s), 1.12 (2H, dd), 1.01 (2H, dd). LCMS RT=0.68 min, M+H+=260.20.

Provenance & Evidence