Reaktion #162715

Reaktionsgleichung

sodium hydroxide

(Z)-ethyl 3-((2-amino-2-oxoethyl)amino)-3-(5-chloro-2-methoxyphenyl)acrylate

butyl acetate

trimethylsilyl isothiocyanate

sodium hydroxide

→

desired product

Ausbeute 53.2%

2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide

Ausbeute 53.2%

Lösungsmittel

methanol water

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeA reaction vessel equipped with an efficient stirrer
2. 2
   Temperaturthe mixture was heated to reflux
3. 3
   workup.WAITAfter 30 min
4. 4
   Sonstigethe organic layer was separated
5. 5
   ExtraktionThe combined aqueous phases were extracted twice with dichloromethane (2×45 mL)
6. 6
   Filtrationfiltered
7. 7
   workup.ADDITIONtreated with 6N HCl until a pH of 2.5
8. 8
   Sonstigethe resulting solid was isolated by vacuum filtration
9. 9
   Temperaturheated
10. 10
    workup.STIRRINGwith stirring at 50° C. for 2 hours
11. 11
    Temperaturcooled to room temperature
12. 12
    Sonstigebefore collecting the solid
13. 13
    Filtrationby vacuum filtration
14. 14
    Sonstigepulling dry
15. 15
    Sonstigedrying in a vacuum oven (20 mm Hg, 50° C.) for 12 hours

Vorschrift

A reaction vessel equipped with an efficient stirrer was charged with (Z)-ethyl 3-((2-amino-2-oxoethyl)amino)-3-(5-chloro-2-methoxyphenyl)acrylate (15 g, 50.2 mmol), butyl acetate (150 mL) and trimethylsilyl isothiocyanate (160.7 mmole, 21.1 g, 22.7 mL) and the mixture was heated to reflux. After 15 hours, the mixture was cooled to 30° C. and treated with 1 N aqueous sodium hydroxide (112.5 mL, 112.5 mmoles). After 30 min, the organic layer was separated and extracted with another portion of 1 N sodium hydroxide (37.5 mL, 37.5 mmoles). The combined aqueous phases were extracted twice with dichloromethane (2×45 mL), filtered, and treated with 6N HCl until a pH of 2.5 was achieved. After stirring for 1 hour, the resulting solid was isolated by vacuum filtration, resuspended in 100 mL of a 1:1 methanol-water solution, heated with stirring at 50° C. for 2 hours, and cooled to room temperature before collecting the solid by vacuum filtration, pulling dry and drying in a vacuum oven (20 mm Hg, 50° C.) for 12 hours to afford 8.7 g of the desired product as a tan solid.

Quelle