Réaction #2075729

Équation de réaction

HCl

Sodium methoxide

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

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

→

solid

Rendement 8.0%

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

Rendement 8.0%

Solvants

MeOH

Conditions de réaction

Traitement

1. 1
   Autrethe reaction
2. 2
   ExtractionThe reaction was extracted with ethyl acetate thrice
3. 3
   Lavagewashed with brine
4. 4
   Autredried
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated
7. 7
   AutreThe product was purified by flash chromatography on silica gel (0-50% EtOAc/hexane) the
8. 8
   Autrerecrystallized from dichloromethane/hexane

Mode opératoire

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).

Source