Methyl iodide → 3-Fluoro-2-methyl-5-(tributylstannyl)pyridine

Temperature

-78 °C

To a mixture of 2,2,6,6-tetramethyl-piperidine (0.30 mL, 1.8 mmol) and 10 mL tetrahydrofuran at −78° C. was dropwise added 2.5 M of n-butyllithium in hexane (0.80 mL). The reaction vessel was then placed into a 0° C. ice bath and stirred for 60 minutes. The reaction vessel was then cooled to −78° C., and 3-fluoro-5-tributylstannylpyridine (504.7 mg, 1.307 mmol) was added as a solution in tetrahydrofuran (2 mL). The reaction mixture was stirred at −78° C. for 90 minutes, and then methyl iodide (0.15 mL, 2.4 mmol) was added. After an additional 30 minutes, the reaction was quenched with saturated aqueous NH4Cl, and extracted with ethyl acetate. The organic extract was dried over MgSO4, filtered, and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (2 g silica, solvent gradient: 0-30% ethyl acetate in heptanes) to yield 381.8 mg (50% pure, 37% yield) of 3-fluoro-2-methyl-5-(tributylstannyl)pyridine. LCMS (ESI): M+H=402.2.

1. customwas then placed into a 0° C.
2. stirringThe reaction mixture was stirred at −78° C. for 90 minutes
3. waitAfter an additional 30 minutes
4. customthe reaction was quenched with saturated aqueous NH4Cl
5. extractionextracted with ethyl acetate
6. extractionThe organic extract
7. dry with materialwas dried over MgSO4
8. filtrationfiltered
9. customevaporated in vacuo
10. customThe crude product was purified via flash chromatography on silica gel (2 g silica, solvent gradient: 0-30% ethyl acetate in heptanes)

ORD record

ord-321c3083a66f4657a9f885a5fff303da

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08623889B2