[F:1][C:2]([F:18])([F:17])[C:3]([NH:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][CH:9]=1)=[O:4].S(=O)(=O)(O)O.[CH2:24]=O>CC(O)=O>[N+:14]([C:11]1[CH:12]=[C:13]2[C:8]([CH2:7][CH2:6][N:5]([C:3](=[O:4])[C:2]([F:17])([F:18])[F:1])[CH2:24]2)=[CH:9][CH:10]=1)([O-:16])=[O:15]2,2,2-Trifluoro-N-[2-(4-nitrophenyl)ethyl]acetamide (21.9 g, 83.4 mmol) was dissolved in HOAc (80 mL) and sulfuric acid (120 mL) and paraformaldehyde (4.0 g, 125 mmol) were added at rt. The solution was stirred at rt for 24 h. The reaction was poured cautiously into approximately 1 L of ice with stirring. The resulting suspension of brown sludge was extracted into EtOAc. The organic was washed with saturated aqueous NaHCO3, brine and dried over MgSO4. The solvent was removed and the brown solid was triturated with hexanes. The brown solid was dried under vacuum and provided 15 g (66%) of the desired tetrahydroisoquinoline product. 1H NMR (400 MHz, DMSO-d6) δ 8.25 (d, J=27.0 Hz, 1H), 8.05 (m, 1H), 7.47 (d, J=8.5 Hz, 1H), 4.88 (d, J=18.1 Hz, 2H), 3.81 (m, 2H), 3.06-2.97 (m, 2H).
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