Cyclopropanamine, 1-(3,4-difluorophenyl)- synthesis

Yield:474709-85-8 56%

Reaction Conditions:

Stage #1: 3,4-Difluorobenzonitrile;ethylmagnesium bromidewith titanium(IV) isopropylate in diethyl ether at -78; for 0.166667 h;
Stage #2: with boron trifluoride diethyl etherate in diethyl ether at -78; for 1 h;

Steps:

14 4.1.14 1-(3,4-Difluorophenyl)cyclopropan-1-amine (18)

To a solution of 3,4-difluorobenzonitrile (278mg, 2mmol) in dry Et₂O (10mL) at-78°C was added dropwise Ti(OiPr)₄ (0.64mL, 2.2mmol) followed by EtMgBr (1.5mL, 2.2mmol, 3M in Et₂O). After 10min, BF₃·Et₂O (0.5mL, 4mmol) was added and the solution was stirred for 1hat-78°C. The reaction was quenched by addition of 1N HCl (2mL) and diluted with Et₂O (10mL). The organic layer was separated, washed with water, brine and dried over MgSO₄. The volatiles were evaporated under reduced pressure and the residue was purified by silica gel column chromatogrpahy using hexanes/EtOAc (1:1) to afford 18 (189mg, 56%). ¹H NMR (400MHz, Chloroform-d) δ 7.16-7.04 (m, 2H), 7.03-6.98 (m, 1H), 1.91 (s, 2H), 1.16-1.05 (m, 2H), 1.01-0.90 (m, 2H). ¹³C NMR (101MHz, Chloroform-d) δ 150.1 (dd, J=247.5, 12.8Hz), 148.6 (dd, J=246.2, 12.8Hz), 144.2 (dd, J=5.0, 3.5Hz), 121.2 (dd, J=6.2, 3.4Hz), 116.9 (d, J=17.0Hz), 114.7 (d, J=17.7Hz), 36.2, 18.2. ¹⁹F NMR (377MHz, Chloroform-d) δ-139.3 to-139.4 (m),-143.3 to-143.4 (m). HRMS (ESI): m/z [M+H]⁺ calcd for C₉H₁₀F₂N: 170.0781, found: 170.0776.

References:

Sari, Ozkan;Boucle, Sebastien;Cox, Bryan D.;Ozturk, Tugba;Russell, Olivia Ollinger;Bassit, Leda;Amblard, Franck;Schinazi, Raymond F. [European Journal of Medicinal Chemistry,2017,vol. 138,p. 407 - 421]