1-(3-FLUORO-PHENYL)-CYCLOPROPYLAMINE synthesis

Yield:-

Reaction Conditions:

Stage #1: m-Fluorobenzonitrile;ethylmagnesium bromidewith titanium(IV) isopropylate in diethyl ether;Inert atmosphere;Schlenk technique;
Stage #2: with boron trifluoride diethyl etherate in diethyl ether;Inert atmosphere;Schlenk technique;

Steps:

3. General Procedures for Synthesis of Starting Materials.

General procedure: Procedure: The preparation of cyclopropylamine was performed according to thereported procedure 8. Ethylmagnesium bromide (10 mmol, 3 M in ether) was added at-70 °C to a solution of a nitrile (5 mmol) and Ti(Oi-Pr)4 (5.5 mmol) in Et2O (25 mL).The yellow solution was stirred for 10 min. After the solution was warmed to rt (1 h),BF3··OEt2 (10 mmol) was added. After the mixture was stirred for 1 h, 1 N HCl (5mL) and ether (25 mL) were added. NaOH (10% aq, 15 mL) was added to the resulting two clear phases and the mixture was extracted with ether. The combinedether layers were dried (Na2SO4), filtered, and concentrated under reduced pressure.The residue was added Et3N (11 mmol, 2.2 equiv) in dichloromethane (25 mL) wasslowly added a solution of pivaloyl chloride (PivCl: 5.5 mmol, 1.1 equiv) from adropping funnel at 0 °C. The reaction mixture was stirred at room temperature for 12h. To the reaction mixture was added saturated aqueous NaHCO3 (10 mL), which wasthen extracted with dichloromethane. The combined organic layers were washed withbrine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purifiedby column chromatography on silica gel with petroleum ether/ethyl acetate to affordthe product.

References:

Wang, Tianhang;Wang, Minyan;Wang, Yandong;Li, Mingjie;Zheng, Yuan;Chen, Qianwei;Zhao, Yue;Shi, Zhuangzhi [Chem,2023,vol. 9,# 1,p. 130 - 142] Location in patent:supporting information