反应详情

Method B. A solution of 4-methoxyaniline (35, 31.0 g, 252 mmol) in water (100 mL) was treated with concentrated aqueous HCl solution (37%, 62 mL, 730 mmol, 2.9 equiv) at 0–5° C. under N2, and the resulting reaction mixture was added dropwise an aqueous solution of sodium nitrite (NaNO2, 20.9 g, 302.4 mmol, 1.2 equiv) in water (50 mL) at 0–5° C. The reaction mixture was subsequently stirred at 0–5° C. for an additional 1.5 h before being transferred into a mixture containing sodium acetate (NaOAc, 47.5 g, 579 mmol, 2.3 equiv), ethyl chloroacetoacetate (41.4 g, 34.8 mL, 252 mmol, 1.0 equiv) in ethyl acetate (200 mL) and water (100 mL) at 0–5° C. The resulting reaction mixture was then stirred at 0–5° C. for 30 min before being warmed up to room temperature for 12 h. When HPLC and TLC showed the reaction was deemed complete, the two layers were separated, and the organic phase was washed with sodium bicarbonate aqueous solution (2×50mL), water (50 mL) and saturated sodium chloride aqueous solution (50 mL), dried over MgSO4, and concentrated in vacuo. The residue was treated with 50% EtOAc/hexane (100 mL) to directly precipitate the crude product. The solids were collected by filtration to afford the crude desired chloro[(4-methoxyphenyl)hydrazono]acetic acid ethyl ester (34, 47.8 g, 64.62 g theoretical, 74%), which was found to be essentially pure to do the following reaction without further purification. This product was found to be identical with the material obtained from method A in every comparable aspect.

1. customthe resulting reaction mixture
2. customThe resulting reaction mixture
3. stirringwas then stirred at 0–5° C. for 30 min
4. customthe two layers were separated
5. washthe organic phase was washed with sodium bicarbonate aqueous solution (2×50mL), water (50 mL) and saturated sodium chloride aqueous solution (50 mL)
6. dry with materialdried over MgSO4
7. concentrationconcentrated in vacuo
8. additionThe residue was treated with 50% EtOAc/hexane (100 mL)
9. customto directly precipitate the crude product
10. filtrationThe solids were collected by filtration