Acetic Anhydride → N-(2-Methyl-1,2,3,4-tetrahydro-7-isoquinolinyl)acetamide

Participants

Reaction Conditions

Reaction Steps

A solution of isoquinoline 252 (2.5 g, 13.0 mmol) in EtOH (200 mL) was stirred with Pd/C (5%, 200 mg) under H2 (35 psi) for 4 h. The solution was filtered through Celite, washed with EtOH (50 mL) and the solvent was evaporated. The residue was dissolved in dioxane (50 mL), Ac2O (2.7 mL, 28.6 mmol) was added and the solution stirred at 20° C. for 16 h. The solvent was evaporated and the residue was partitioned between dilute aqueous NH3 solution (50 mL) and DCM (50 mL). The aqueous layer was extracted with DCM (4×125 mL), the combined organic fraction dried and the solvent evaporated. The residue was purified by chromatography, eluting with 5% MeOH/DCM, to give acetamide 253 (2.1 g, 77%) as a brown solid: mp 157-159° C.; 1H NMR δ 7.29 (br s, 1H, H-8), 7.27 (br s, 1H, H-6), 7.22 (br s, 1H, NH), 7.12 (br d, J=8.1 Hz, 1H, H-5), 4.18 (d, J=16.2 Hz, 1H, H-1), 3.82 (d, J=16.1 Hz, 1H, H-1), 3.11-3.25 (m, 2H, H-3), 2.91-3.00 (m, 2H, H-4), 2.61 (s, 3H, NCH3), 2.16 (s, 3H, COCH3); 13C NMR δ 168.3, 136.6, 131.0, 129.2, 126.6, 119.2, 118.1, 61.5, 56.6, 47.3, 24.5, 24.0; MS (APCI) m/z 205 (MH+, 100%). Anal. calcd for C12H16N2O.½CH3OH.½H2O: C, 65.5; H, 8.4; N, 12.2. Found: C, 65.8; H, 8.8; N, 12.6%.

Provenance & Evidence