Triethylamine → 5-(Chloromethyl)isoquinoline

Participants

Reaction Steps

To a solution of 0.1212 g (0.76 mmol) 15 in 8 mL CH2Cl2 at 0° C. was added 64.8 μL (0.84 mmol) methanesulfonyl chloride and 84.7 μL (0.61 mmol) triethylamine. After 3 h at 0° C., the reaction mixture was warmed to room temperature and 32.0 μL (0.23 mmol) triethylamine added. The reaction was recooled to 0° C., and 14.7 μL (0.19 mmol) methanesulfonyl chloride and 26.5 μL (0.19 mmol) triethylamine were added. After 62 h at room temperature, the reaction mixture was diluted with 25 mL CH2Cl2 and washed with 10 mL saturated NaHCO3 solution. The aqueous layer was extracted with 10 mL CH2Cl2, and the combined organic layers were washed with 10 mL brine, dried over Na2SO4, filtered and concentrated in vacuo. The product was purified by flash chromatography (15×140 mm silica gel, 2% (10% NH40H:MeOH):CH2Cl2). Mixed fraction repurified by flash chromatography (12×75 mm silica gel, 1% (10% NH40H:MeOH):CH2Cl2) to give 16. 1H NMR (CDCl3, 400 MHz) δ 9.305 (s, 1H, ArH); 8.653 (d, 1H, J=5.85 Hz, ArH); 7.992 (d, 1H, J=8.23 Hz, ArH); 7.927 (d, 1H, J=5.94 Hz, ArH); 7.753 (d, 1H, J=7.04 Hz, ArH); 7.583 (dd, 1H, J=7.14, 8.14 Hz, ArH); 5.020 (s, 1H, ArCH2); MS (Electrospray): m/z 177.9, 179.9 (M+H, 35Cl, 37Cl).

Provenance & Evidence