Diethyl (ethoxymethylene)malonate → Ethyl 4-hydroxy-2-methylpyrimidine-5-carboxylate

Acetamidine hydrochloride (37.16 g, 0.39 mole) was stirred in sodium ethoxide in ethanol (73 mL of a 21% solution, 0.20 mole) for 5 minutes. Diethyl ethoxymethylenemalonate (31.5 mL, 0.15 mole) was added, and the reaction mixture was refluxed for 5 hours. The reaction mixture was allowed to cool to room temperature overnight, and diluted with dichloromethane (100 mL). The solution was filtered, washing the solid cake with dichloromethane. The filtrate was concentrated at reduced pressure. The residue was dissolved in dichloromethane (150 mL) and 2.0N HCl (30 mL). The pH of the aqueous layer was 1. The organic layer was washed with water, saturated sodium bicarbonate and brine, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue was dissolved in hot dichloromethane (50 mL). Ethyl acetate was added (50 mL). The product precipitated. The solution was boiled for 5 minutes, cooled to room temperature, and hexanes were added (50 mL). The resulting crystals were filtered, then washed with ethyl acetate (20 mL) followed by hexanes (50 mL) to yield the title compound (7.22 g, 27%) as off-white crystals. Rf=0.27 (silica gel, 10% isopropanol in dichloromethane). The title compound also was prepared by the route described in Example 102.

1. temperaturethe reaction mixture was refluxed for 5 hours
2. filtrationThe solution was filtered
3. washwashing the solid cake with dichloromethane
4. concentrationThe filtrate was concentrated at reduced pressure
5. dissolutionThe residue was dissolved in dichloromethane (150 mL)
6. washThe organic layer was washed with water, saturated sodium bicarbonate and brine
7. dry with materialdried over anhydrous magnesium sulfate
8. customthe solvent was removed under reduced pressure
9. dissolutionThe residue was dissolved in hot dichloromethane (50 mL)
10. additionEthyl acetate was added (50 mL)
11. customThe product precipitated
12. temperaturecooled to room temperature
13. additionhexanes were added (50 mL)
14. filtrationThe resulting crystals were filtered
15. washwashed with ethyl acetate (20 mL)

ORDレコード

ord-6d810bc27017435d996d4344c6e5b714

出典データセット

uspto-grants-2002_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06342504B1