反应 #2075729

反应方程式

HCl

Sodium methoxide

2-ethoxy-3-oxo-succinic acid diethyl ester

4-chloro-2-fluoro-3-methoxybenzamidine hydrochloride

→

solid

收率 8.0%

2-(4-Chloro-2-fluoro-3-methoxyphenyl)-5-ethoxy-6-hydroxypyrimidine-4-carboxylic acid methyl ester

收率 8.0%

溶剂

MeOH

反应条件

后处理

1. 1
   其他the reaction
2. 2
   萃取The reaction was extracted with ethyl acetate thrice
3. 3
   洗涤washed with brine
4. 4
   其他dried
5. 5
   过滤filtered
6. 6
   浓缩concentrated
7. 7
   其他The product was purified by flash chromatography on silica gel (0-50% EtOAc/hexane) the
8. 8
   其他recrystallized from dichloromethane/hexane

实验过程

Sodium methoxide (12 mL, 62.74 mmol) was added dropwise to a solution of 2-ethoxy-3-oxo-succinic acid diethyl ester (9.7 g of 75% purity, 31.37 mol), 4-chloro-2-fluoro-3-methoxybenzamidine hydrochloride (5 g, 20.91 mol) and MeOH (24 mL). The reaction was allowed to stir for 1 hour. The reaction was cooled to 0° C. and 1 N HCl was added to acidify the reaction. The reaction was extracted with ethyl acetate thrice. The organic extracts were combined, washed with brine, dried, filtered and concentrated. The product was purified by flash chromatography on silica gel (0-50% EtOAc/hexane) the recrystallized from dichloromethane/hexane to give a white solid (623mg, 8% yield): mp 173-175° C.: 1H NMR (CDCl3) δ 11.28 (br s, 1H), 7.78 (dd, 1H), 7.31 (dd, 1H), 4.35 (q, 2H), 4.02 (s, 3H), 3.98 (s, 3H), 1.38 (t, 3H).

来源