Chloroacetyl chloride → 1-[7-(2-chloro-acetyl)-3,4-dihydro-1H-isoquinolin-2-yl]-2,2,2-trifluoro-ethanone

Participants

Reaction Steps

To a suspension of AlCl3 (24.16 g) in CH2Cl2 (162 ml) was added chloroacetyl chloride (15 ml) dropwise at 0-5° C. under argon for 20 min and left to warm to room temperature. To this mixture was added compound (4) (9.29 g, 40 mmol) over a period of 30 min at room temperature. The resulting mixture was then stirred for an additional 3 hours and poured onto a mixture of ice-cold water (407 ml). The mixture was stirred for 5 min, and the layers were separated. The aqueous layer was extracted with CH2Cl2 (2×200 ml). The combined organic layers were washed with water (2×240 ml) and 5% aqueous NaHCO3 (3×240 ml). The organic layer was dried and the solvent evaporated to give a white solid (5) (10.47 g, 88%). TLC Rf=0.4 (n-hexane/EtOAc=3:1). mp: 120-122° C. 1H NMR (300 MHz, CDCl3) (NMR, Varian Gemini): δ 7.78 (q, J=4 Hz, 1H, Aryl H), 7.34-7.26 (m, 2H, Aryl Hs), 4.87 (s, 2H, Ph-CH2—N), 4.67 (s, 2H, —CH2—C═O), 3.95-3.87 (m, 2H, —CH2—N), 3.06-3.01 (m, 2H, Ph-CH2—)—. Fast Atom Bombardment Mass Spectrometry (FABMS) m/z: 306 (M+1) (C13H11NO2ClF3).

Provenance & Evidence