Tetrahydrofuran → 4,6-Dimethoxy-2-(methylsulfonyl)pyrimidine

A stirred solution of 143.6 grams (0.772 mole) of 4,6-dimethoxy-2-methylthiopyrimidine in 460 mL of tetrahydrofuran was cooled to 10°-15° C., and a cloudy solution of 525.0 grams (0.849 mole) of 80% monoperoxyphthalio acid, magnesium salt hexahydrate in 600 mL of methanol was added at a rate to maintain the reaction mixture temperature below 15° C. Upon completion of the addition, which required one hour, the reaction mixture was cooled, and 500 mL of aqueous 1M sodium sulfite solution was added dropwise to destroy excess peroxides present in the reaction mixture. Upon completion of addition, the reaction mixture was stirred for 15 minutes and then was concentrated under reduced pressure to a residue. The residue was stirred in 2500 mL of ethyl acetate and 1500 mL of water. The layers were separated, and the aqueous layer was extracted with 450 mL of ethyl acetate. The ethyl acetate layers were combined and washed with one 500 mL portion of water, two 350 mL portions of aqueous 20% potassium carbonate, two 350 mL portions of water, and one 300 mL portion of an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to yield 123.3 grams of 4,6-dimethoxy-2-methylsulfonylpyrimidine; m.p. 126°-127.5° C. The reaction was repeated several times.

1. temperatureto maintain the reaction mixture temperature below 15° C
2. additionUpon completion of the addition, which required one hour
3. temperaturethe reaction mixture was cooled
4. customto destroy excess peroxides present in the reaction mixture
5. additionUpon completion of addition
6. concentrationwas concentrated under reduced pressure to a residue
7. stirringThe residue was stirred in 2500 mL of ethyl acetate
8. customThe layers were separated
9. extractionthe aqueous layer was extracted with 450 mL of ethyl acetate
10. washwashed with one 500 mL portion of water, two 350 mL portions of aqueous 20% potassium carbonate, two 350 mL portions of water, and one 300 mL portion of an aqueous solution saturated with sodium chloride
11. dry with materialThe organic layer was dried with magnesium sulfate
12. filtrationfiltered
13. concentrationThe filtrate was concentrated under reduced pressure

ORD record

ord-25d448cb267d4dcb959bb0a2bcc2429c

Source dataset

uspto-grants-1992_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05149357