1,4-Dioxaspiro[4.5]decan-8-one → HCID 67499969, compound

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Reaction Steps

To a −60° C. solution of n-butyl lithium (23 mL, 2.5M in hexane, 58.2 mmol) in diethyl ether (40 mL) was added a solution of 2-bromo-3-chloropyridine (Alfa, 8.0 g, 41.6 mmol) in diethyl ether (60 mL) over 15 minutes. The reaction mixture was stirred for 40 minutes followed by a slow addition (about 15 minutes) of a solution of 1,4-dioxaspiro[4.5]decan-8-one (Aldrich, 8.44 g, 54.0 mmol) in diethyl ether (100 mL), and stirred until reaction mixture warmed up to ambient temperature (about 3 hours). The mixture was quenched with saturated NH4Cl, diluted with ethyl acetate and washed with water. The organic layer was separated, concentrated and the residue crystallized from ethyl acetate-hexanes to obtain 5.5 g of the title compound. Two more crystallizations of the mother liquors yielded 1.61 g more material. Total yield 7.13 g (64%). 1H NMR (300 MHz, DMSO-d6) δ ppm 1.59 (d, J=12.69 Hz, 2H), 1.80 (d, J=12.69 Hz, 2H), 1.94 (td, J=12.69, 4.36 Hz, 2H), 2.30-2.41 (m, 2H), 3.88 (s, 4H), 5.36 (s, 1H), 7.36 (dd, J=7.93, 4.76 Hz, 1H), 7.88 (dd, J=7.93, 1.59 Hz, 1H), 8.48 (dd, J=4.76, 1.59 Hz, 1H). MS (DCI) m/z 270.10 (M+H)+.

Provenance & Evidence