2,2,6,6-Tetramethylpiperidine → HCID 86677186, compound

Temperature

-30 °C

2,2,6,6-tetramethylpiperidine (1.729 g, 2.066 mL, 12.24 mmol) was dissolved in THF (20.00 mL) and cooled to −30° C. under nitrogen. BuLi (4.488 mL of 2.5 M, 11.22 mmol) was added dropwise and the reaction allowed to warm to 0° C. Stir at this temperature for 10 minutes then cooled to −78° C. A solution of 2-fluoropyrazine (1 g, 10.20 mmol) in THF (4.000 mL) was added slowly and the mixture stirred at −78° C. for 1 h. Methyl 6-chloropyridine-2-carboxylate (1.750 g, 10.20 mmol) in THF (6.000 mL) was added dropwise at between −78 and −70° C., stirred at −78° C. for 1 h. Reaction quenched with 5% citric acid at −78° C. then allow to warm to ambient temperature. Diluted with EtOAc and separated layers. Extracted with EtOAc (x1) then wash combined organics with NaHCO3 (x1), brine (x1). Dried (MgSO4), filtered and concentrated. Crude product purified by ISCO companion (80 g SiO2, 0 to 50% EtOAc/petrol) to leave title compound as an orange oil (1.12 g, 46%). 1H NMR (DMSO-d6) δ 7.90 (dd, 1H), 8.22-8.15 (dd, 2H), 8.67 (dd, 1H), 8.84 (dd, 1H). ES+238.13.

1. temperatureto warm to 0° C
2. temperaturethen cooled to −78° C
3. stirringthe mixture stirred at −78° C. for 1 h
4. stirringstirred at −78° C. for 1 h
5. customReaction
6. customquenched with 5% citric acid at −78° C.
7. temperatureto warm to ambient temperature
8. additionDiluted with EtOAc
9. customseparated layers
10. extractionExtracted with EtOAc (x1)
11. washthen wash
12. dry with materialDried (MgSO4)
13. filtrationfiltered
14. concentrationconcentrated
15. customCrude product purified by ISCO companion (80 g SiO2, 0 to 50% EtOAc/petrol)

ORD record

ord-8a66f6120d9e4cea93ae0a8d974758d2

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08895740B2