Hydrochloric Acid → 3-Trifluoromethyl-pyrazine-2-carboxylic acid (9-isopropyl-1,2,3,4-tetrahydro-1,4-methano-naphthalen-5-yl)-amide

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Reaction Steps

To a 1-ml vial containing 9-isopropyl-1,2,3,4-tetrahydro-1,4-methano-naphthalen-5-ylamine (6) (0.1 g, 0.497 mmol) and DCM (Volume: 2 mL) was added a 2.0 M solution of trimethylaluminum (0.017 g, 0.243 mmol). After evolution of gas ceased, methyl 3-(trifluoromethyl)pyrazine-2-carboxylate (8) (0.113 g, 0.546 mmol) was added as a solution in dichloromethane (0.5 ml) and the mixture was stirred at room temperature overnight. The reaction mixture was poured into 2N HCl (5 ml) and after bubbling ceased, was extracted with dichloromethane (2×5 ml) and was passed through a Biotage phase separator. The organic extracts were combined and the solvent was removed. The residue was loaded onto a silica column and was eluted using a ethyl acetate/hexanes gradient to afford the title compound (0.15 g, 80%) as a white solid with 4:1 syn:anti product: mp 173-177° C.; 1H NMR (600 MHz, CDCl3) δ 9.33 (s, 1H), 8.90 (d, J=2.2 Hz, 1H), 8.86 (d, J=2.3 Hz, 1H), 7.97 (d, J=8.4 Hz, 1H), 7.20-7.14 (m, 1H), 7.06 (d, J=7.2 Hz, 1H), 3.40 (s, 1H), 3.28 (s, 1H), 2.02-2.00 (m, 2H), 1.65 (d, J=10.0 Hz, 1H), 1.32-1.18 (m, 2H), 1.05-0.98 (m, 1H), 0.84 (d, J=6.6 Hz, 6H); ESIMS m/z 376.3 ([M+H]+), m/z 374.4 ([M−H])−).

Provenance & Evidence