| 37% |
Stage #1: With sodium ethanolate In ethanol at 55℃;
Stage #2: With sodium ethanolate In ethanol |
Sodium (356 mg, 15.5 mmol) was carefully added to ethanol (5.9 mL) to prepare sodium ethoxide solution in ethanol. The above freshly prepared ethanol solution (3.5 mL) was added to a stirred suspension of propionimidamide hydrochloride (1.05 g, 9.69 mmol). The mixture was warmed to 55 °C, then the heating bath was removed and a solution of mucobromic acid (1 g, 3.87 mmol) in ethanol was added dropwise at a rate which maintained a constant temperature, followed by a further sodium ethoxide solution (2 mL). After cooling, the mixture was filtered and evaporated to a residue which was shaken vigorously with hydrochloric acid (2 M x 2.4 mL). The brown precipitate was filtered off and washed with cold water, then freeze-dried to give 5-Bromo-2-ethylpyrimidine-4- carboxylic acid (330 mg, 37percent) as a yellow solid. LCMS: 231 [M+l]+, 1H NMR (400 MHz, DMSO-de): δ 1.25 (t, J= 7.6 Hz, 3H), 2.88 (q, J= 7.6 Hz, 2H), 9.05 (s, 1H). |
| 37% |
at 55℃; |
Sodium (356 mg, 15.5 mmol) was carefully added to ethanol (5.9 mL) to prepare sodium ethoxide solution in ethanol. The above freshly prepared ethanol solution (3.5 mL) was added to a stirred suspension of propionimidamide hydrochloride (1.05 g, 9.69 mmol). The mixture was warmed to 55° C., then the heating bath was removed and a solution of mucobromic acid (1 g, 3.87 mmol) in ethanol was added dropwise at a rate which maintained a constant temperature, followed by a further sodium ethoxide solution (2 mL). After cooling, the mixture was filtered and evaporated to a residue which was shaken vigorously with hydrochloric acid (2 M×2.4 mL). The brown precipitate was filtered off and washed with cold water, then freeze-dried to give 5-Bromo-2-ethylpyrimidine-4-carboxylic acid (330 mg, 37percent) as a yellow solid. LCMS: 231 [M+1]+, 1H NMR (400 MHz, DMSO-d6): δ 1.25 (t, J=7.6 Hz, 3H), 2.88 (q, J=7.6 Hz, 2H), 9.05 (s, 1H). |
| 37% |
With sodium ethanolate In ethanol at 55℃; |
Sodium (356 mg, 15.5 mmol) was added carefully ethanol (5.9 mL) to prepare a sodium ethoxide solution in ethanol. Freshly prepared ethanol solution of above-described (3.5mL), was added to a stirred suspension of propionamide imide amide hydrochloride (1.05g, 9.69mmol). The mixture was allowed to warm to 55 , then, the heating bath was removed Mukoboron acid in ethanol (1g, 3.87mmol) was dropped in the solution the rate at which a constant temperature is maintained, and then, further sodium ethoxide solution (2mL ) was added. After cooling, evaporated residue by filtration future was vigorously shaken with hydrochloric acid (2Mx2.4mL). The brown precipitate was removed by filtration, and washed with cold water and then lyophilized to give 5-bromo-2-ethyl-4-carboxylate as a yellow solid (330mg, 37percent). |