Phosphorus oxychloride → 2-Methoxy-4,6-dimethyl-5-nitropyrimidine

Temperature

100 °C

4,6-Dimethyl-5-nitropyrimidin-2-ol (18.4 g, 108 mmol) wad added portionwise to a stirred phosphoryl chloride (3.0 mL) at 0° C., and the mixture was stirred at 100° C. for 80 min. The mixture was concentrated in vacuo, and methanol (180 mL) was added to the residue carefully at 0° C. Sodium methoxide (28% solution in methanol, 68.8 g, 357 mmol) was added dropwise to a stirred mixture at 0° C., and the mixture was stirred at 0° C. for 10 min. The mixture was diluted with aqueous saturated ammonium chloride and concentrated in vacuo. The residue was diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 5-20% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the title compound as a yellow wax (13.0 g, 71.0 mmol, 66%).

1. concentrationThe mixture was concentrated in vacuo, and methanol (180 mL)
2. additionwas added to the residue carefully at 0° C
3. stirringthe mixture was stirred at 0° C. for 10 min
4. concentrationconcentrated in vacuo
5. additionThe residue was diluted with water
6. extractionextracted with ethyl acetate
7. washThe combined organic layer was washed with brine
8. dry with materialdried over anhydrous magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe residue was purified by flash column chromatography on silica gel eluting with a 5-20% ethyl acetate/n-hexane gradient mixture
12. concentrationThe filtrate was concentrated in vacuo

ORD record

ord-4dfbfb696bcd4357b5f87275abe7e2e8

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901141B2