Methanesulfonic Acid → 7-Bromo-2-methyl-4-p-tolyl-1,2,3,4-tetrahydroisoquinoline

Participants

Reaction Conditions

Reaction Steps

Methane sulfonic acid (30 mL, 480 mmol) was added dropwise via addition funnel to a mixture of the product from Step B (4.58 g, 8.57 mmol) in 1,2-dichloroethane (80 mL) at 40° C. After the addition was completed, the reaction mixture was heated at 40° C. for an additional hour. The cooled reaction mixture was poured over ice and made basic to pH 9 with concentrated ammonium hydroxide. The reaction mixture was extracted with ethyl acetate (4×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by column chromatography (120 g silica; 90:10 hexane/ethyl acetate) provided 7-bromo-2-methyl-4-p-tolyl-1,2,3,4-tetrahydroisoquinoline (1.05 g, 40%). This product was resolved by chrial HPLC (Chiralpak AD, 95:5 heptane/isopropanol with 0.1% diethylamine). The (+)enantiomer (430 mg, 41%) was obtained as a clear oil: [α]25d+11.9° (0.2, methanol); 1H NMR (500 MHz, CDCl3) δ 7.22 (s, 1H), 7.16 (d, J=8.3 Hz, 1H), 7.09 (d, J=7.9 Hz, 2H), 7.04 (d, J=8.1 Hz, 2H), 6.74 (d, J=8.5 Hz, 1H), 4.03-3.98 (m, 1H), 3.70 (d, J=15.0 Hz, 1H), 3.56 (d, J=15.0 Hz, 1H), 3.01-2.98 (m, 1H), 2.53-2.49 (m, 1H), 2.40 (s, 3H), 2.32 (s, 3H).

Provenance & Evidence