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 (6 volumes) was charged and followed by aluminum chloride (1.03 eq) 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 onto 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 formed was diluted with 2-propanol (1 volume) and then heated to reflux to form a solution. Heptane (2.9 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 heptane and dried at not more than 40° C. to yield approximately 75% of compound 8 as an off-white to light pink solid. 1H NMR (CDCl3) δ 7.66 (s, 1H), 7.18 (td, 1H, J=7 Hz, 2 Hz), 6.88-6.98 (m, 2H), 6.42 (s, 1H), 3.89-3.92 (m, 5H), 3.85 (s, 3H), 2.55 (s, 3H).

Provenance & Evidence