Hydrochloric Acid → HCID 23000617, compound

Participants

Reaction Conditions

Reaction Steps

Through a 0° C. solution of 0.218 g (0.496 mmol) ethyl {2-[(tert-butoxycarbonyl)(2,2-difluoro-2-pyridin-2-ylethyl)amino]-3-fluoropyridin-4-yl}acetate 29-1 in 10 mL EtOAc was passed a steady stream of HCl gas for 10 min. The reaction was stirred at 0° C. for 1.5 h and then at room temperature for 10 min. The reaction mixture was then flushed with N2 and poured onto 150 mL EtOAc/50 mL 2M NaOH/7 mL conc NaOH. The layers were mixed and then separated. The aqueous layer was back extracted with 50 mL EtOAc. The combined organics were washed w/50 mL water and 50 mL brine, dried over Na2SO4, filtered, and concentrated in vacuo. Purification by automated flash chromatography (40 g silica cartridge, linear gradient 0-50% EtOAc/hexane over 30 min, 30 mL/min flow rate) gave ethyl {2-[(2,2-difluoro-2-pyridin-2-ylethyl)amino]-3-fluoropyridin-4-yl}acetate 29-2. 1H NMR (CDCl3, 400 MHz) δ8.663 (d, 1H, J=4.67 Hz, ArH); 7.829-7.790 (m, 2H, ArH); 7.693 (d, 1H, J=7.14 Hz, ArH); 7.377 (t, 1H, J=6.14 Hz, ArH); 6.489 (t, 1H, J=4.99 Hz, ArH); 4.492-4.405 (m, 2H, CH2); 4.199-4.145 (m, 2H, CH2); 3.585 (s, 2H, CH2); 1.276-1.237 (m, 3H, CH3); MS (Electrospray): m/z 340.1 (M+H).

Provenance & Evidence