Dichloromethane → 1-[5-(3-Chloro-2-fluorobenzyl)-2,4-dimethoxyphenyl]ethanone

Participants

Reaction Conditions

Reaction Steps

The compound 5 DCM solution was transferred into a clean reactor and cooled to −13 to −7° C. Dichloromethane (3 volumes) was charged and then aluminum chloride (1.03 eq) was added to this solution while maintaining the temperature at not more than −7° C. Acetyl chloride (1.12 eq) was slowly charged to the mixture while maintaining the temperature at not more than −10° C. The reaction mixture was agitated at −13 to −7° C. and the progress of the acylation reaction was monitored by HPLC. After the acylation was completed the reaction mixture was transferred into 5 volumes of cold (2 to 8° C.) water while maintaining the temperature at not more than 25° C. The quenched mixture was allowed to warm to 19 to 25° C. and agitated till a biphasic mixture was formed. The organic phase was separated and washed with water (3 volumes). The organic phase was separated and concentrated by vacuum distillation. The solvent was exchanged to 2-propanol by coevaporation under vacuum. The slurry that formed was diluted with 2-propanol (1 volume) and then heated to reflux to form a solution. Heptane (2.92 volumes) was slowly charged to the hot solution and cooled to 0 to 5° C. to form a slurry. The product was isolated by filtration. The wet cake was washed with a mixture of 2-propanol and heptanes and dried at not more than 40° C. to yield approximately 85% of compound 8 as off-white to light pink solid.

Provenance & Evidence