Tetrahydrofuran → HCID 86610910, compound

Participants

Reaction Conditions

Reaction Steps

In a 500 mL 3-neck round bottom flask equipped with septa, magnetic stir bar thermocouple, addition funnel and nitrogen line was placed a solution of tert-butyl (3R,4S)-3-{[3,5-bis(trifluoromethyl)benzoyl]oxy}-4-(4-fluorophenyl)pyrrolidine-1-carboxylate (product step A, 17.77 mmol) in 115 mL anhydrous THF. The solution was cooled to 0° C. with an ice/water bath. To the cooled solution was slowly added 45 mL (21.32 mmol) of a 0.5M solution of Tebbe reagent in toluene (commercially available) dropwise by addition funnel. After the addition was complete the funnel was rinsed with anhydrous toluene then THF and the resulting solution added to the reaction mixture. After stirring 1.5 h at 0° C., an additional 9.0 mL (4.5 mmol, 0.25 equiv.) of 0.5M solution of Tebbe reagent in toluene was added dropwise by addition funnel. The reaction was stirred an additional 15 min then carefully quenched by addition of 15 mL water drop by drop. The resulting mixture was transferred to a separatory funnel and extracted with ether/EtOAc. The organic layers were combined, dried over anhydrous sodium sulfate, filtered and the solvent removed under vacuum. The residue dissolved in a minimal amount of methylene chloride filtered and the solvent removed under vacuum. The resulting oil was purified by column chromatography on silica gel eluting EtOAc/hexanes gradient (5/95 to 10/90) to afford the title compound as a yellow foam. 1H-NMR (CDCl3): δ: 1.54 (s, 9H), 3.46-4.01 (br. m, 6H), 4.0 (d, 1H), 4.61 (s, 1H), 4.91 (d, 1H), 7.08 (m, 2H), 7.22 (m, 2H), 7.83 (s, 1H), 8.0 (s, 2H)ppm.

Provenance & Evidence