2-(triMethylsilyl)ethyl 4-(trifluoroMethylsulfonyloxy)-5,6-dihydropyridine-1(2H)-carboxylate

Synthesis

A 1 M solution of bis(trimethylsilyl)aminolithium/THF (485 mL) was diluted with dry tetrahydrofuran (1 L) under a nitrogen atmosphere and the solution was cooled to -78 °C. A solution of 2-(trimethylsilyl)ethyl 4-oxopiperidine-1-carboxylate (106 g, 436 mmol) in anhydrous tetrahydrofuran (400 mL + 75 mL of rinse solution) was added dropwise to the stirred solution over a period of 55 min. 45 min later, an anhydrous N-phenylbis(trifluoromethylsulfonyl)imide (158.8 g, 445 mmol) in anhydrous tetrahydrofuran (700 mL + 50 mL rinse solution) solution. After reacting at -78 °C for 1 h, the reaction mixture was transferred to an ice bath and continued for 3 h, followed by vacuum concentration. The residue was diluted with water and the aqueous layer was extracted twice with a solvent mixture of ether/cyclohexane (1:1). The organic layers were combined, dried with anhydrous magnesium sulfate and allowed to stand overnight in a refrigerator. After vacuum concentration, 158.6 g (97% yield) of tert-butyl 2-(trimethylmethylsilyl)ethyl 4-(((trifluoromethyl)sulfonyl)oxy)-5,6-dihydropyridine-1(2H)-carboxylate was obtained, the product was an amber colored oil.1H NMR (CDCl3) δ 5.78 (broad single peak, 1H), 4.21 (multiple peaks, 2H), 4.10 (multiple peaks , 2H), 3.68 (triple peak, 2H, J = 5.3Hz), 2.46 (multiple peaks, 2H), 1.02 (multiple peaks, 2H), 0.05 (single peak, 9H).

References

[1] Patent: WO2004/60884, 2004, A1. Location in patent: Page 23-24
[2] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 8, p. 2859 - 2872
[3] Patent: WO2004/60884, 2004, A1. Location in patent: Page 19-20
[4] Patent: WO2011/79102, 2011, A1. Location in patent: Page/Page column 26-27
[5] Patent: WO2011/78984, 2011, A1. Location in patent: Page/Page column 27