2-Phenylacetophenone → HCID 19101430, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred ice-cold (0° C.) solution of 10 g (0.1 mole) diisopropylamine in 100 ml of anhydrous THF under nitrogen gas is added, dropwise, 40 ml (2.5 M) n-butyllithium over a period of about 15 min to form lithium diisopropylamine solution, which is a pale yellow. To the amine solution is added 8.8 g (0.1 mole) N,N-dimethylacetamide in 10 ml THF, dropwise, via syringe, over a period of 10 min. The resulting lithium enolate of N,N-dimethylacetamide solution is deep yellow, and is stirred for 45 min at 0° C. A solution of 18.5 g (0.095 mole) benzylphenylketone in 20 ml of THF is added rapidly over a period of about 2 min to the enolate solution. An orange N,N-dimethyl-3,4-diphenyl-3-hyroxybutyramide solution is formed, and is stirred at 0° C. for about 15 min. Then 40 ml (2.5 M) n-butyllithium is added dropwise via syringe to form a deep red dianion solution. The dianion solution is stirred at about -20° C. for 30 min. Methyl bromide (19 g, 0.2 mole, 2 equivalents) in 20 ml THF is added slowly to methylate the dianion. The resulting N,N-dimethyl-2-methyl-3,4-diphenyl-3-hydroxybutyramide mixture is held at about -20° C. for about 1 h, and a cloudy yellow suspension is formed. The suspension is warmed to room temperature (25° C.), then quenched with 200 ml of a 0° C. solution of 2 N HCl, which is added with rapid stirring. The quenched, pale yellow solution is diluted with 200 ml ether. The organic layer is recovered and washed with brine and dried over anhydrous MgSO4. The mixture is filtered, yielding a pale yellow solution of N,N-dimethyl-2-methyl-3,4-diphenyl-3-hydroxybutyramide, which is reduced in the following step.

Provenance & Evidence