Water → HCID 86686333, compound

Temperature

-78 °C

4-iodo-2-methoxy-3,5-dimethylpyridine (2.0 g) in THF (40 mL) was cooled to −78° C. A 2.69 M solution of n-butyllithium in hexane (6.5 mL) was added dropwise to the solution over 10 minutes. The mixture was stirred at −78° C. for 20 minutes. Triisopropyl borate (5.26 mL) was added dropwise to the mixture over five minutes. The mixture was stirred with warming to 20° C. over 1.5 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The aqueous layer was neutralized with citric acid. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate. The desiccant was removed by filtration, and the filtrate was then concentrated under reduced pressure. The residue was triturated by adding MTBE. The precipitated solid was collected by filtration. This solid is called first crop. The filtrate was concentrated under reduced pressure. The residue was triturated by adding MTBE. The precipitated title compound (551 mg) was collected by filtration. The first crop were suspended in ethyl acetate. Trituration was performed by adding a small amount of MTBE. The precipitated title compound (553.3 mg) was collected by filtration. The filtrate was concentrated under reduced pressure. The residue was triturated by adding MTBE. The precipitated title compound (121:1 mg) was collected by filtration. The combined title compound (1.23 g) was obtained.

1. stirringThe mixture was stirred
2. temperaturewith warming to 20° C. over 1.5 hours
3. extractionfollowed by extraction with ethyl acetate
4. extractionThe aqueous layer was extracted with ethyl acetate
5. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
6. customThe desiccant was removed by filtration
7. concentrationthe filtrate was then concentrated under reduced pressure
8. customThe residue was triturated
9. additionby adding MTBE
10. filtrationThe precipitated solid was collected by filtration
11. concentrationThe filtrate was concentrated under reduced pressure
12. customThe residue was triturated
13. additionby adding MTBE
14. customThe precipitated title compound (551 mg)
15. filtrationwas collected by filtration
16. additionby adding a small amount of MTBE
17. customThe precipitated title compound (553.3 mg)
18. filtrationwas collected by filtration
19. concentrationThe filtrate was concentrated under reduced pressure
20. customThe residue was triturated
21. additionby adding MTBE
22. customThe precipitated title compound (121:1 mg)
23. filtrationwas collected by filtration
24. customwas obtained

ORD record

ord-5a4eeded47864f9abd3954bef6b5101e

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08563565B2