Boron trifluoride → 1-(5-Fluoro-2-methylphenyl)propan-2-amine

Participants

Reaction Steps

Borontrifluoride diethyletherate (272.68 g, 1.921 mol) was added dropwise through an additional funnel to a mixture of NaBH4 (58.14 g, 1.537 mol) in 600 mL of anhydrous THF cooled in a cooling bath under an argon atmosphere. After addition, the mixture was warmed to rt and continued to stir for 30 minutes. A solution of 4-fluoro-1-methyl-2-(2-nitroprop-1-enyl)benzene (60 g, 0.307 mol) in 200 mL of anhydrous THF was added dropwise through an additional funnel to the above mixture. The resulting reaction mixture was heated at reflux for 6-7 h under an argon atmosphere. After the end of the reaction was established by TLC, the reaction mixture was cooled to rt, quenched by water, acidified by concentrated HCl, and heated to 80° C. for 4 h. The mixture was washed with diethyl ether twice. The aqueous layer was separated, basified with 10% aqueous NaOH solution, and extracted with diethyl ether until no or a little product is left in aqueous layer. The combined extracts were dried over anhydrous MgSO4, filtered, evaporated and purified by a silica gel column chromatography using CH2Cl2 and methanol (85:15 v/v) as eluent to give 43.3 g of the designed compound as off-white solid. 1H NMR (500 MHz, DMSO-d6) δ 7.89 (br s, 2H, NH2), 7.22-7.20 (m, 1H, ArH), 7.03-6.96 (m, 2H, ArH), 3.40-3.34 (m, 1H, CH), 2.91-2.87 (m, 1H, CH), 2.69-2.65 (m, 1H, CH), 2.24 (s, 3H, CH3), 1.10 (d, J=6.5 Hz, 3H, CH3); Mass (ESI, positive) m/z 168.0 [M+H]+.

Provenance & Evidence