2,2,6,6-Tetramethylpiperidine → 2-Fluoro-3-(tributylstannyl)pyrazine

Temperature

0 °C

n-Butyllithium (1.6 M in hexane, 0.920 mL, 10.99 mmol) was added to 2,2,6,6-tetramethylpiperidine (2.024 mL, 11.99 mmol) in THF (50 mL) at −50° C. Following the addition, the mixture was stirred at 0° C. for 20 min and then cooled down to −100° C. 2-Fluoropyrazine (980 mg, 9.99 mmol) in THF (5 mL) was then added dropwisely. After 5 min, tributyltin chloride (3.25 mL, 11.99 mmol) in THF (5 mL) was added dropwisely and stirring was continued for 1 h. The reaction was quenched with a solution of 35% aqueous HCl, ethanol, THF (1:4:5) and allowed to warm to 20° C. The reaction mixture was diluted with sat. aqueous NaHCO3 (30 mL) and extracted with EtOAc (2×50 mL). The organic extract was washed with saturated aqueous NaCl (30 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as orange oil. The crude material was adsorbed onto a plug of silica gel and purified by chromatography through a silica gel column eluting with 50% CH2Cl2/hexanes to give 2-fluoro-3-(tributylstannyl)pyrazine (2980 mg, 7.70 mmol, 77% yield) as colorless oil. 1H NMR (300 MHz, CDCl3) δ 8.63 (s, 1H); 8.02 (s, 1H); 1.46-1.68 (m, 6H); 1.12-1.42 (m, 12H); 0.88 (t, J=7.23 Hz, 9H).

1. additionthe addition
2. temperaturecooled down to −100° C
3. waitAfter 5 min
4. stirringstirring
5. waitwas continued for 1 h
6. customThe reaction was quenched with a solution of 35% aqueous HCl, ethanol, THF (1:4:5)
7. temperatureto warm to 20° C
8. additionThe reaction mixture was diluted with sat. aqueous NaHCO3 (30 mL)
9. extractionextracted with EtOAc (2×50 mL)
10. extractionThe organic extract
11. washwas washed with saturated aqueous NaCl (30 mL)
12. dry with materialdried over Na2SO4
13. filtrationThe solution was filtered
14. concentrationconcentrated in vacuo
15. customto give the crude material as orange oil
16. custompurified by chromatography through a silica gel column
17. washeluting with 50% CH2Cl2/hexanes

ORD record

ord-a4fc86ee43e549f291e6619897e7d750

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08362241B2