Triisopropyl phosphite → (4S)-4-benzyl-3-{[(1R,2R)-2-(4-chlorophenyl)-4-methylenecyclopentyl]carbonyl}-1,3-oxazolidin-2-one

Participants

Reaction Steps

An oven-dried 250 mL round bottom flask equipped with a magnetic stir bar and a septum, was charged with 4.705 g (13.7 mmol) of the product of Step A, 0.185 g (0.82 mmol) of palladium acetate, and 27 mL anhydrous tetrahydrofuran. The reaction mixture was freed of air by alternate cycles of degassing in vacuo and flushing with nitrogen using an external manifold attached through tubing to a needle inserted through the septum of the flask. To the brick red suspension was then added 3.80 mL (3.334 g, 17.9 mmol) 2-[(trimethylsilyl)methyl]-2-propen-1-yl acetate followed by 1.02 mL (0.860 g, 4.13 mmol) of triisopropyl phosphite. The reaction mixture was heated to reflux and stirred under nitrogen for 3 h at which point TLC analysis (15% ethyl acetate-hexanes) revealed consumption of the starting material and production of two new products. The reaction mixture was cooled to room temperature, transferred to a separatory funnel and partitioned between water and diethyl ether. The organic layer was washed with water, brine, dried (MgSO4), filtered and evaporated in vacuo. The product mixture was purified on a Biotage Flash 40i chromatography apparatus (90 g Flash 40M silica gel cartridge) eluted with 10% ethyl acetate-hexanes which afforded a less polar and a more polar product. Evaporation of the fractions containing the more polar product and drying in vacuo afforded 2.12 g of the title compound.

Provenance & Evidence