(3R)-1-((1R,2R)-2-Hydroxycyclohex-1-yl)-2,5-dioxopyrrolidin-3-yl acetate → 2,5-dioxopyrrolidin-3-(R)-yl acetate

Participants

Reaction Conditions

Reaction Steps

To a chilled (0° C.) solution of (3R)-1-((1R,2R)-2-hydroxylcyclohex-1-yl)-2,5-dioxopyrrolidin-3-yl acetate (15.0 g, 58.7 mmol) in anhydrous dichloromethane (100 mL) was added tetrafluoroboric acid diethyl ether complex (3.2 mL). The resultant reaction mixture was stirred at 0° C. for 20 minutes before adding a solution of 2-(3-benzyloxy-4-methoxy-phenyl)-ethyl-2,2,2-trichloroacetimidate (24.8 g, 61.6 mmol, 1.05 equiv.) in dichloromethane (100 mL) via an addition funnel over 30 minutes. The reaction mixture was stirred at 0° C. until the reaction was judged complete by HPLC analysis. The reaction mixture was quenched with water (250 mL). The organic layer was separated from the aqueous layer and subsequently washed with dilute NaHCO3 (5% wt solution, 2×100 mL), and water (5×100 mL). The organic layer was dried (anhydrous MgSO4), filtered, and concentrated under reduced pressure to ˜100 mL solution. The solution was cooled at −20° C. for 24 hours and the precipitate (trichloroacetamide) was removed by filtration. The filtrate was further concentrated to a volume of ˜40 mL. This process was repeated three times until the bulk of the by-product (trichloroacetamide) was removed. After the third filtration, the filtrate was concentrated in vacuo to give (1R, 2R)-12-[2-(3-benzyloxy-4-methoxy-phenyl)ethoxy]cyclohexyl}-2,5-dioxopyrrolidin-3-(R)-yl acetate as a pale yellow syrup (25 g, 86% yield).

Provenance & Evidence