反应详情

温度

70 °C

To a stirred mixture of 2-bromo-6-chlorobenzoic acid (20 g, 85 mmol), methylacetoacetate (310 ml, excess), and copper (I) bromide 12.2 g, 85 mmol) sodium hydride (8.5 g, 212 mmol, 60% in oil) was added by portions and then heated at 70° C. for 16 hours. The resulting mixture was diluted with water (600 ml) and extracted with diethyl ether (3×500 ml). Aqueous phase was acidified with 2M HCl and extracted with ethyl acetate (2×800 ml). The combined organic solution was washed with brine (100 ml), dried (Na2SO4) and evaporated. The obtained oil was treated with a hot mixture of ethyl acetate (20 ml) and heptane (200 ml) and decanted for 2 times, dried in vacuo to give 8 g of yellow-brown solid, yield 34%. 1H NMR (500 MHz, DMSO-d6): 1.73 (s, 3H), 3.6 (s, 3H), 7.24 (d, 1H), 7.44 (t, 2H), 7.5 (d, 1H), 12.85 (s, 1H, OH of enol form), 13.4 (br, 1H, CO2H).

1. additionwas added by portions
2. extractionextracted with diethyl ether (3×500 ml)
3. extractionextracted with ethyl acetate (2×800 ml)
4. washThe combined organic solution was washed with brine (100 ml)
5. dry with materialdried (Na2SO4)
6. customevaporated
7. additionThe obtained oil was treated with a hot mixture of ethyl acetate (20 ml) and heptane (200 ml)
8. customdecanted for 2 times
9. customdried in vacuo