Реакция #2075729

Уравнение реакции

HCl

Sodium methoxide

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

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

→

solid

Выход 8.0%

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

Выход 8.0%

Растворители

MeOH

Условия реакции

Обработка

1. 1
   Другоеthe reaction
2. 2
   ЭкстракцияThe reaction was extracted with ethyl acetate thrice
3. 3
   Промывкаwashed with brine
4. 4
   Другоеdried
5. 5
   Фильтрацияfiltered
6. 6
   Концентрированиеconcentrated
7. 7
   ДругоеThe product was purified by flash chromatography on silica gel (0-50% EtOAc/hexane) the
8. 8
   Другоеrecrystallized from dichloromethane/hexane

Методика

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).

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