Sulfuric Acid → HCID 68856339, compound

A slurry of 5-amino-3-methyl-2-methylsulfanylpyridine (20.3 g, 132 mmol) in 20 wt percent aqueous sulfuric acid (170 mL) was cooled to −2° C. via an ice/salt water bath. A solution of sodium nitrite (9.1 g, 132 mmol) in water (30 mL) was added dropwise, maintaining the internal temperature at or below 1° C. After stirring for an additional 20 minutes, the reaction mixture was cautiously poured in portions into a rapidly stirred, hot (100° C.) solution of 20 wt. percent aqueous sulfuric acid (330 mL). Stirring was continued for 10 minutes, then the mixture was allowed to cool to room temperature. The reaction was washed with methylene chloride (3×200 mL), then the pH of aqueous layer was raised to 4-5 (in the cold) with 50 wt percent aq. sodium hydroxide (ca. 160 mL). A precipitate consisting of both a white solid and a reddish brown oil had formed. Additional 20 wt percent aq. sodium hydroxide was added, raising the pH to 6 and resulting in more precipitate/oil formation. The mixture was cooled and filtered, collecting the white solid, while the majority of colored oil remained in the mother liquor. The collected solid was taken up in 5 percent aq. sodium hydroxide (300 mL) and washed with ether (2×100 mL) to remove impurities and unreacted starting material. The aqueous portion was then treated with activated charcoal, filtered through celite, and the pH adjusted to 5-6 with glacial acetic acid. The precipitate was collected by filtration and dried in vacuo affording an off-white powder, 14 g, 90 mmol, 68 percent yield.

1. temperaturemaintaining the internal temperature at or below 1° C
2. additionthe reaction mixture was cautiously poured in portions into
3. stirringa rapidly stirred
4. stirringStirring
5. waitwas continued for 10 minutes
6. washThe reaction was washed with methylene chloride (3×200 mL)
7. temperaturethe pH of aqueous layer was raised to 4-5 (in the cold) with 50 wt percent aq. sodium hydroxide (ca. 160 mL)
8. customa reddish brown oil had formed
9. temperatureraising the pH to 6
10. customresulting in more precipitate/oil formation
11. temperatureThe mixture was cooled
12. filtrationfiltered
13. customcollecting the white solid
14. washwashed with ether (2×100 mL)
15. customto remove impurities
16. additionThe aqueous portion was then treated with activated charcoal
17. filtrationfiltered through celite
18. filtrationThe precipitate was collected by filtration
19. customdried in vacuo
20. customaffording an off-white powder, 14 g, 90 mmol, 68 percent yield

ORD record

ord-59dff358eb83485dbd3fe7498e88bb62

Source dataset

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07531482B2