Synthesis
6a) A hexane solution of 2.4 M n-butyllithium (92.0 mL, 230 mmol) was slowly added dropwise to a solution containing monoethyl malonate (13.6 mL, 115 mmol) and a catalytic amount of 2,2'-bipyridine at -55 to -65 °C. After the dropwise addition, cyclopentanecarbonyl chloride (7.0 mL, 58 mmol) was added in batches. The reaction mixture was gradually warmed to room temperature with stirring and subsequently poured into a mixture of 1N aqueous hydrochloric acid solution and ether. The organic layer was separated, washed three times with saturated sodium bicarbonate solution, dried over anhydrous magnesium sulfate, concentrated and then purified by silica gel column chromatography (eluent: 0-5% ethyl acetate in hexane solution with gradient elution) to afford ethyl 3-cyclopentyl-3-oxopropanoate (9.50 g, 89% yield).1H-NMR (400 MHz, DMSO-d6) δ 4.06 (q, J = 7 Hz. 2H), 3.60 (s, 2H), 2.99-2.91 (m, 1H), 1.78-1.47 (m, 8H), 1.15 (t, J = 7 Hz, 3H).
References
[1] Patent: US2008/96921, 2008, A1. Location in patent: Page/Page column 42
[2] Journal of Medicinal Chemistry, 1998, vol. 41, # 17, p. 3186 - 3201
