4-ISOPROPYLPHENETHYLAMINE HYDROCHLORIDE synthesis

Yield:61035-87-8 35%

Reaction Conditions:

Stage #1: (4-isopropylphenyl)acetonitrilewith lithium aluminium tetrahydride in diethyl ether at 0; for 1 h;Heating / reflux;
Stage #2: with water;ammonium chloride in diethyl ether at 0;
Stage #3: with hydrogenchloride in methanol at 20; for 0.583333 h;

Steps:

120

Intermediate 120; (2-[4-(I -methylethyl)phenyllethyl)amine hydrochloride; A solution of LiAIH4 (838 mg, 20.97 mmol) in diethyl ether (15 ml) was cooled at 0⁰C under argon. [4-(1-methylethyl)phenyl]acetonitrile (Intermediate 119) (1.67 g, 10.48 mmol) in solution of diethyl ether (10 ml) was added drop by drop at 0⁰C. The mixture was stirred at reflux for 1 hour. The mixture was cooled at 0°C, NH₄CI (1.246 g) was added and 1.2 ml of water was added. Diethyl ether was added and the mixture was dried overMgSO₄ and filtered on celite and washed with diethyl ether. The filtrate was evaporated. The residue was diluted with a solution of methanol saturated with HCI (25 ml) to formed chlorhydrate. The mixture was stirred at room temperature 35 min. The mixture was evaporated and co-evaporated with dichloromethane. The obtained solid was triturated with a mix of dichloromethane/diethyl ether to give the title compound as a pale yellow solid (734 mg, 35%).NMR¹H NMR (300 MHz), DMSO δ : 7.18 (m, 4H), 2.98 (m, 2H), 2.84 (m, 2H), 2.50 (m, 1 H), 1.17 (d, 6H).

References:

WO2009/47240,2009,A1 Location in patent:Page/Page column 84-85