Sodium Hydroxide → Hydrochloric Acid

Participants

Reaction Steps

To a solution of 4-((4-Methylphenyl)methyl)amino-1-phenylmethylpiperidine (800 mg, 2.7 mmol) in dry dichloromethane (30 ml) was added diisopropylethylamine (1.5 ml)followed by 4-methoxyphenylacetyl chloride (997 mg, 5.4 mmol). The reaction mixture was stirred at room temperature. After 16 h, the reaction mixture was concentrated, redissolved in diethyl ether, and extracted with HCl (0.6 N). The aqueous layer was isolated, treated with NaOH (1 N)until basic, and extracted with dichloromethane (20 ml). The organic layer was isolated and dried (Na2SO4), filtered, and concentrated, and redissolved in diethyl ether. The hydrochloride was formed by addition of HCl (4 M in dioxane), and recrystallized from diethyl ether to give the title compound. Yield: 600 mg, 50%; 1H-NMR (CDCl3): δ 1.75 (d, 2 H), 2.32 (s, 3 H), 2.50 (q, 2 H), 2.70 (q, 2 H), 3.38 (d, 2 H), 3.54 (s, 2 H), 3.78 (s, 3 H), 4.06 (d, 2 H), 4.54 (s, 2 H), 4.82 (m, 1 H), 6.78-7.60 (aromatic protons, 13 H); 13C-NMR (CDCl3): δ 21.0, 26.0, 40.3, 46.3, 49.0, 51.8, 55.3, 60.8, 114.2, 125.6, 126.6, 127.9, 129.4, 129.60, 129.62, 130.3, 131.4, 134.8, 137.1, 158.7, 172.9; Mp. 197-200° C.; Elemental analysis: Found C, 71.29; H, 7.25; N, 5.73; calcd for hydrate: C, 71.37; H, 7.43; N, 5.74.

Provenance & Evidence