HCID 117992217, compound → HCID 117992057, compound

Participants

Reaction Conditions

Reaction Steps

(R)-tert-butyl 4-(5-(4-(benzyloxy)-4-oxobutan-2-yl)-6-chloropyrimidin-4-yl)piperazine-1-carboxylate (1710 g) was dissolved in THF (4.0 L) and placed in a nitrogen-purged 5 gallon autoclave. Isopropanol (6.0 L) was added. The reaction mixture was sparged with nitrogen gas 5 times (25 psi), and the autoclave was heated to 35-40° C. A slurry of palladium acetate (81 g) and dppp (163 g) in isopropanol (2.0 L) was added at 40-45° C. and stirred. The reaction mixture was sparged with nitrogen gas 3 times (25 psi) and stirred for 20 minutes at 40-45° C. to dissolve the solids. A slurry of potassium carbonate, 325 mesh (299 g) in isopropanol (2.0 L) was added at 40-45° C. with stirring. The reaction mixture was sparged with nitrogen gas 5 times (25 psi), then sparged with carbon monoxide gas 5 times (40 psi). The autoclave was sparged with carbon monoxide gas to 55 psi. The reaction mixture was stirred at 50° C. and 55 psi (carbon monoxide gas) for a minimum of 50 hours and monitored by TLC and HPLC. The reaction mixture was cooled to room temperature and transferred into a filtration bottle. Silica gel (400 g) and Celite® (400 g) were added, and the reaction mixture was stirred open to air for 2 hours. The reaction mixture was filtered using a silica gel pad (1000 g) in a scintered funnel (D×H, 8×14 inches) and washed with ethyl acetate (4-5 L) and concentrated under vacuum to yield the product as viscous dark brown oil (contains residual dppp[O]2. Yield=1900 g (˜100%, contains residual dppp[O]2), structure confirmed by 1H-NMR (CDCl3).

Provenance & Evidence