Hydrochloric Acid → Ethyl 4-{[tert-butyl(diphenyl)silyl]oxy}-3-oxobutanoate

Participants

Reaction Conditions

Reaction Steps

To a 1-L round-bottom flask equipped with a magnetic stir-bar, addition funnel, low temperature thermometer with thermometer adapter and a N2 inlet was added monoethyl malonate (14.53 g, 0.1 moles, 2 eq) in dry THF (150 ml, 0.73M) and 20 mg of 2,2′-dipyridyl. After cooling the reaction mixture to −78° C. (dry ice/acetone), n-BuLi (2.5M in Hexanes, 88 ml, 0.22 moles, 4 eq) was added at a rate to maintain the internal temperature below −10° C. Once the addition was complete the reaction was allowed to warm to −10° C. by removal of the cold bath. The reaction remained a light pink color; this designates that there was ample amount of n-BuLi to deprotonate the monoethyl malonate. (If the color had turned yellow the reaction would have had to have been re-cooled to −78° C. and additional n-BuLi would have had to have been added followed be re-warming to −10° C.) At this point the reaction mixture was cooled to −78° C. followed by the dropwise addition of neat {[tert-Butyl(diphenyl)silyl]oxy}acetyl chloride (18 g, 54 mmoles, 1 eq) over a period of 15 minutes maintaining the internal reaction temperature below −60° C. This was allowed to stir at −78° C. for 10 minutes at which point the reaction was transferred to a separatory funnel containing diethyl ether (900 ml) and 1N HCl (450 ml). This was agitated and vented until further gas evolution ceased after which the phases were separated and the organic phase was washed with saturated sodium bicarbonate, brine and dried over Na2SO4. This was then filtered, concentrated in vacuo and purified by silica gel chromatography (5% EtOAc/Hexanes to 20% EtOAc/Hexanes) to yield 12.2 g (60%) of product.

Provenance & Evidence