Hydrochloric Acid → HCID 131716331, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of KHMDS (potassium hexamethyldisilazane) (4.96 moles) in toluene (8 L) and THF (8 L) at -78° C. under N2 was added dropwise the ketone of Step B (1.36 kg, 4.8 moles) in THF (1500 ml) over 21/2 hours. The reaction mixture was stirred 1 hour at -78° C. Methyl bromoacetate (520 ml, 5.6 moles) in THF (800 ml) was added dropwise over 1-1/2 hours. After stirring 1 hour at -78° C. the reaction mixture was poured with stirring into 16 L of HCl (lN). The organic layer was separated and the aqueous layer was further extracted with ethyl acetate (4 L). The combined organic layers were evaporated. The residue was dissolved in a mixture of THF (6 L) and EtOH (6 L), and NaOH (3 L, 2.6M) was added. After stirring 2 hours at room temperature the homogeneous reaction mixture was concentrated in vacuo to remove THF and EtOH. The aqueous residue was extracted with ethyl acetate (2×2 L). The aqueous layer was cooled in ice-water and acidified with concentrated HCl (approximately 800 ml). Extraction with ethyl acetate (1×4 L, 1×1 L), drying (Na2SO4) and evaporation afforded the title acid as a tan, oily solid, m.p. 9220 -96° C., which was used as is in Step D.

Provenance & Evidence