89.4% |
With palladium 10% on activated carbon; ammonium formate; In methanol; at 55℃; for 16h; |
[00537] A mixture of 81(2.00 g, 9.43 mmols, 1.0 eq), Pd/C (10%, 1.0 g), HCOONH4 (1.2 g, 18.9 mmols, 2.0 eq.) in MeOH (20 mL) was heated to 55 C for 16 hours. The reaction mixture was cooled to room temperature, filtered through celite, and the filtrate was concentrated. The residue was partitioned between ethyl acetate (100 mL) and NaOH (4% in water, 30 mL). The organic layer were washed with brine, dried over Na2SO4, filtered, and concentrated to afford the desired product 82 (1.50 g, 8.38 mmols, 89.4%) as a yellow oil. |
85% |
With ammonium formate;palladium 10% on activated carbon; In methanol; at 55℃; for 16h; |
3-Amino-6-trifluoromethoxypyridine (52); At 25 0C, palladium (10% on charcoal, 700 mg) was added with stirring to a solution of 3-amino-2-chloro-6-trifluoromethoxypyridine (51, 1.3 g, 6.1 mmol, 1 eq) and ammonium formate (770 mg, 12.1 mmol, 2 eq) in methanol (20 mL). The reaction mixture was stirred for 16 h at 55 0C before being filtrated under suction and the filtrate evaporated. The residue was partitioned between ethyl acetate (2chi 30 mL) and an aqueous solution of sodium hydroxide (4%, 30 mL). The combined organic layers were dried over sodium sulfate before being evaporated to afford pure 3-amino-6- trifluoromethoxypyridine (52, 920 mg, 5.2 mmol, 85%) as colorless crystals; m.p. 31-330C.1H NMR (CDCl3, 300 MHz): delta = 7.66 (d, J= 2.9 Hz, 1 H), 6.97 (dd, J= 8.6, 2.9 Hz, 1 H), 6.76 (d, J = 8.6, 1 H), 3.55 (bs, 2 H). - 19F NMR (CDCl3, 282 MHz): delta = -57.7 - 13C NMR (CDCl3, 75 MHz): delta = 148.8, 141.6, 133.9, 125.8, 120.3 (q, J = 257 Hz), 114.3. - C6H5F3N2O (178): calcd. (%) C 40.46, H 2.83, N 15.73; found C 40.00, H 2.92, N 15.37. |