Triethylamine → N-Methyl 3-(S)-(3,4-dichlorophenyl)-5-hexen-2-(RS)-amine

Participants

Reaction Conditions

Reaction Steps

A mixture of 102 mg (0.42 mmol) of 3-(S)-(3,4-dichloro-phenyl)-5-hexen-2-one (from Step 2 above), 170 mg (2.52 mmol) of methylamine hydrochloride, and 234 μl (1.68 mmol) of triethylamine in 4.0 mL of methanol was treated with 16 mg (0.25 mmol) of sodium cyanoborohydride and stirred at 22° C. for 20 hours. Saturated aqueous sodium bicarbonate solution (1.0 mL) was added and the resulting milky mixture was diluted with 5.0 mL of ethyl acetate and 5.0 mL of water. The layers were separated and the organic layer was washed with water (3×5 mL). The aqueous layers were extracted with 10 mL of ethyl acetate. The combined organic layers were washed with 10 mL of saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography on 42 g of silica gel using 10:1 v/v ether/ hexane as the eluant afforded 64 mg of the higher Rf isomer (Isomer A) and 22 mg of a lower Rf isomer (Isomer B) both as yellow oils. 1H NMR (400 MHz, CDCl3); Isomer A: δ 1.04 (d, 3H), 2.29-2.35 (m, 4H), 2.50-2.68 (m, 3H), 4.86-4.95 (m, 2H), 5.48-5.56 (m, 1H), 7.01 (dd, 1H), 7.26 (d, 1H), 7.34 (d, 1H); Isomer B: δ 0.86 (d, 3H), 2.32-2.50 (m, 4H), 2.51-2.53 (m, 1H), 2.68-2.73 (m, 2H), 4.88-4.98 (m, 2H), 5.54-5.61 (m, 1H), 6.97 (dd, 1H), 7.22 (d, 1H), 7.33 (d, 1H). Mass Spectrum (Isomer A) (FAB): m/z 260 (M+H, 37Cl+35Cl isotope, 70%), 258 (M+H, 35Cl+35Cl isotope, 100%).

Provenance & Evidence