2-(3,4-DIFLUOROPHENYL)PROPAN-2-AMINE synthesis

Yield:306761-17-1 51%

Reaction Conditions:

with cerium(III) chloride in tetrahydrofuran;diethyl ether at -25; for 1 h;

Steps:

16 4.1.16 2-(3,4-Difluorophenyl)propan-2-amine (20)

A solution of anhydrous CeCl₃ (2.84g, 11.5mmol) in THF (18mL) was stirred at 45°C for 3h and cooled down to room temperature. Then, 3,4-difluorobenzonitrile (800mg, 5.75mmol) was added and the mixture was cooled down to-25°C before addition of MeLi (9.6mL, 14.4mmol, 1.5M in Et₂O). The solution was stirred 1hat-25°C and quenched with NaOH 30% (4mL). The mixture was stirred for 16hat room temperature and the cerium salts were filtered and washed with THF. The filtrate was dried over MgSO₄ and concentrated under reduced pressure. The residue was dissolved in THF and HCl (4N in dioxane) was added and the solution was concentrated in vacuo. The resulting salts were filtered, washed with hexanes and then treated with aqueous ammonium hydroxide (5mL). The solution was then extracted with CH₂Cl₂, dried over MgSO₄ and concentrated in vacuo. The residue was purified by silica gel column chromatography using CH₂Cl₂/ MeOH (98:2) to afford 20 (502mg, 51%). ¹H NMR (400MHz, Chloroform-d) δ 7.41-7.32 (m, 1H), 7.27-7.19 (m, 1H), 7.11 (dt, J=10.2, 8.4Hz, 1H), 1.49 (s, 6H). ¹³C NMR (101MHz, Chloroform-d) δ 150.51 (dd, J=121.6, 12.6Hz), 148.83-147.43 (m), 147.48 (d, J=16.9Hz), 120.69 (dd, J=6.1, 3.5Hz), 116.62 (d, J=16.8Hz), 114.26 (d, J=17.8Hz), 52.12 (d, J=1.4Hz), 33.01. ¹⁹F NMR (377MHz, Chloroform-d) δ-139.4 to-139.5 (m),-143.4 to-143.5 (m). HRMS (ESI): m/z [M+H]⁺ calcd for C₉H₁₂F₂N: 172.0938, found: 172.0932.

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]