Diethyl Malonate → HCID 178516650, compound

A solution of fluoroacetonitrile (11 g) in ethanol (10.9 mL)-diethyl ether (186 mL) was bubbled with hydrogen chloride under ice-cooling until the solution was saturated with hydrogen chloride with stirring, and the mixture was stirred at the same temperature for 4 hours. The precipitated crystals were collected by filtration. The collected crystals were washed with diethyl ether, and dried under reduced pressure to give ethyl 2-fluoroacetimidate hydrochloride (24.9 g). This material was suspended in ethanol (50 mL). To the suspension was added ethanol (130 mL) containing ammonia (about 5 g), and the mixture was stirred at room temperature overnight. The crystals were collected by filtration. The collected crystals were washed with diethyl ether, and dried under reduced pressure to give 2-fluoroacetamidine hydrochloride (16.3 g). To a mixture of sodium methoxide (28% methanol solution, 83.6 mL) and methanol (145 mL) was added 2-fluoroacetamidine hydrochloride (16.3 g), followed by adding diethyl malonate (22.0 mL), and the mixture was heated at reflux for 11 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added water (145 mL). The mixture was acidified by adding concentrated hydrochloric acid (18 mL), and the mixture was stirred at room temperature for 30 minutes. The precipitated crystals were collected by filtration. The collected crystals were washed with water and diethyl ether, and dried under reduced pressure to give 2-fluoromethyl-4,6-dihydroxypyrimidine (20.1 g). To a mixture of fuming nitric acid (36 mL) and acetic acid (18 mL) was added 2-fluoromethyl-4,6-dihydroxypyrimidine (20.1 g) slowly under ice-cooling, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was cooled in ice. To the mixture was added cold water, and the mixture was stirred at room temperature for 1 hour. The precipitated crystals were collected by filtration. The collected crystals were washed with water and diethyl ether, and dried under reduced pressure to give the title compound (16.8 g).

1. temperaturethe mixture was heated
2. temperatureat reflux for 11 hours
3. concentrationThe reaction mixture was concentrated under reduced pressure
4. additionTo the residue was added water (145 mL)
5. additionby adding concentrated hydrochloric acid (18 mL)
6. filtrationThe precipitated crystals were collected by filtration
7. washThe collected crystals were washed with water and diethyl ether
8. customdried under reduced pressure

ORD record

ord-2e5799a21723477a851e32742c73bf64

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08217069B2