Reaction #164712

Reaction equation

sodium hydroxide

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

butyl acetate

trimethylsilyl isothiocyanate

sodium hydroxide

→

desired product

Yield 53.2%

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

Yield 53.2%

Solvents

methanol water

Conditions

Workup

1. 1
   OtherA reaction vessel equipped with an efficient stirrer
2. 2
   Temperaturethe mixture was heated to reflux
3. 3
   workup.WAITAfter 30 min
4. 4
   Otherthe organic layer was separated
5. 5
   ExtractionThe 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
   Otherthe resulting solid was isolated by vacuum filtration
9. 9
   Temperatureheated
10. 10
    workup.STIRRINGwith stirring at 50° C. for 2 hours
11. 11
    Temperaturecooled to room temperature
12. 12
    Otherbefore collecting the solid
13. 13
    Filtrationby vacuum filtration
14. 14
    Otherpulling dry
15. 15
    Otherdrying in a vacuum oven (20 mm Hg, 50° C.) for 12 hours

Procedure

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.

Source