4,6-Dichloro-2-ethoxypyrimidine

To a suspension of NaH (60percent, 536 mg, 13.4 mmol) in dry THF (20 mL) was added EtCH(617 mg, 13.4 mmol) at 0 °C under N2. The suspension was stirred at 0 °C for 1 h. Then, the suspension was cooled to -78 °C and a solution of 4, 6-dichloro-2-methanesulfonyl- pyrimidine (2.03 g, 8.90 mmol) in THE (20 mL) was added to the stirring mixture slowly, then the mixture was stirred at -78 °C for 1 h. Sat. NH4CI solution (10 mL) and EtOAc (40 mL) was added. The organic layer was dried and concentrated in vacuo. The residue waspurified by column (PE: EtOAc = 50: 1) to give the title compound (1.62 g, yield 94percent) as a colorless oil.1H NMR (300 MHz, CDCI3): ö 7.01 (s, 1 H), 4.45 (q, J = 7.2 Hz, 2H), 1.41(1, J = 7.2 Hz, 3H).500mL was added 43.5g of the reaction flask equipped with a stirrer and a thermometer 2-methanesulfonyl-4, 6-dichloropyrimidine (0.19 mol) and 90g of ethanol was stirred at room temperature, then cooled to 0 deg.] C, was added dropwise 130g a concentration of 20wtpercent solution of sodium ethoxide (0.38mol). After incubation the reaction dropwise IH, sampled and analyzed to the feedstock <1percent the reaction was stopped. After adjusting the pH about neutral reaction system a small amount of acetic acid, recovering ethanol pressure, dichloromethane was distilled off and after addition of water, stirring layers were separated and the organic layer was washed with water once, after the first solvent is recovered under reduced pressure and normal pressure, until no liquid outflow of the desired product product was obtained 35.2g of 2-ethoxy-4, 6-dichloropyrimidine, yield 95.2percent, purity 96.5percent (HPLC).500mL was added 43.5g of the reaction flask equipped with a stirrer and a thermometer 2-methanesulfonyl-4, 6-dichloropyrimidine (0.19 mol) and 90g of ethanol was stirred at room temperature, then cooled to 0 deg.] C, was added dropwise 130g a concentration of 20wt% solution of sodium ethoxide (0.38mol). After incubation the reaction dropwise IH, sampled and analyzed to the feedstock <1% the reaction was stopped. After adjusting the pH about neutral reaction system a small amount of acetic acid, recovering ethanol pressure, dichloromethane was distilled off and after addition of water, stirring layers were separated and the organic layer was washed with water once, after the first solvent is recovered under reduced pressure and normal pressure, until no liquid outflow of the desired product product was obtained 35.2g of 2-ethoxy-4, 6-dichloropyrimidine, yield 95.2%, purity 96.5% (HPLC).To a suspension of NaH (60%, 536 mg, 13.4 mmol) in dry THF (20 mL) was added EtCH(617 mg, 13.4 mmol) at 0 C under N2. The suspension was stirred at 0 C for 1 h. Then, the suspension was cooled to -78 C and a solution of 4, 6-dichloro-2-methanesulfonyl- pyrimidine (2.03 g, 8.90 mmol) in THE (20 mL) was added to the stirring mixture slowly, then the mixture was stirred at -78 C for 1 h. Sat. NH4CI solution (10 mL) and EtOAc (40 mL) was added. The organic layer was dried and concentrated in vacuo. The residue waspurified by column (PE: EtOAc = 50: 1) to give the title compound (1.62 g, yield 94%) as a colorless oil.1H NMR (300 MHz, CDCI3): oe 7.01 (s, 1 H), 4.45 (q, J = 7.2 Hz, 2H), 1.41(1, J = 7.2 Hz, 3H).To a solution of 2. 4, 6-Dichloro-2-ethoxypyrimidine Recovery 4, 6-Dichloro-2-ethoxypyrimidine was prepared from 4, 6-dihydroxy-2-ethoxypyrimidine essentially as described in and the distillation residue obtained after conversion of the chlorophosphoric acid by-products to phosphorus oxychloride and distillation of the reaction mixture to remove the phosphorus oxychloride was analyzed by liquid phase chromatography. The components of the distillation residue observed by ultraviolet absorption detection were found to include about 91.8 percent the desired product and about 4.1 percent 2, 4, 6-trichloropyrimidine. The distillation residue was added to water with vigorous stirring. There was an exotherm. Sufficient 45 percent aqueous potassium hydroxide solution was then added with stirring to bring the pH of the aqueous phase of the mixture to 12.8, the pressure was reduced to about 80 mm Hg (about 11 kiloPascals), and the mixture was heated to 50 C. The triethylamine liberated by the addition of the potassium hydroxide was removed by distillation. The organic phase of the distillation residue was separated from the aqueous phase by decantation and was analyzed by liquid chromatography. It was found to be about 96.8 percent the title compound uncontaminated with 2, 4, 6-trichloropyrimidine, which was not detected.2. 4, 6-Dichloro-2-ethoxypyrimidine Recovery 4, 6-Dichloro-2-ethoxypyrimidine was prepared from 4, 6-dihydroxy-2-ethoxypyrimidine essentially as described in and the distillation residue obtained after conversion of the chlorophosphoric acid by-products to phosphorus oxychloride and distillation of the reaction mixture to remove the phosphorus oxychloride was analyzed by liquid phase chromatography. The components of the distillation residue observed by ultraviolet absorption detection were found to include about 91.8 percent the desired product and about 4.1 percent 2, 4, 6-trichloropyrimidine. The distillation residue was added to water with vigorous stirring. There was an exotherm. Sufficient 45 percent aqueous potassium hydroxide solution was then added with stirring to bring the pH of the aqueous phase of the mixture to 12.8, the pressure was reduced to about 80 mm Hg (about 11 kiloPascals), and the mixture was heated to 50C. The triethylamine liberated by the addition of the potassium hydroxide was removed by distillation. The organic phase of the distillation residue was separated from the aqueous phase by decantation and was analyzed by liquid chromatography. It was found to be about 96.8 percent the title compound uncontaminated with 2, 4, 6-trichloropyrimidine, which was not detected.

Molecular Weight:193.03
XLogP3:2.8
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:191.9857182
Monoisotopic Mass:191.9857182
Topological Polar Surface Area:35
Heavy Atom Count:11
Complexity:115
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes