Citric Acid → HCID 22319400, compound

Participants

Reaction Conditions

Reaction Steps

Lithium bis(trimethylsilyl)amide (244 ml, 1M in tetrahydrofuran, 244 mmol) was added dropwise over an hour to a cooled (−75° C.) solution of tert-butyl 2-oxo-1-piperidinecarboxylate (J. Org. Chem. 1983, 48, 2424; J. Chem. Soc. I, 1989, 721) (48.7 g, 244 mmol) in tetrahydrofuran (200 ml) under nitrogen, so as to maintain the temperature below −70° C. The mixture was warmed to 0° C., stirred for 90 minutes, then re-cooled to −75° C. A solution of the imidazole from preparation 66 (26.0 g, 188 mmol) in tetrahydrofuran (86 ml) was added dropwise over 30 minutes, and once addition was complete, the reaction was stirred for 2 hours at −75° C. The mixture was poured into 15% aqueous citric acid solution (650 ml), and extracted with ethyl acetate (3×250 ml). The aqueous solution was basified to pH 8 using 10% sodium hydroxide, and extracted with dichloromethane (3×250 ml). These organic extracts were dried and concentrated under reduced pressure to give the title compound as a pale yellow solid, 54.1 g.

Provenance & Evidence