Carbon Dioxide → HCID 19035084, compound

Participants

Reaction Steps

A small (4 mg) sample of diphenylacetic acid was dissolved in 50 mL of tetrahydrofuran and stirred at room temperature. To this solution was slowly added dropwise n-butyllithium as a 2.5M hexane solution until the solution turned light yellow from the diphenylacetic acid dianion. This protocol ensures that the solution is dry. At this point the solution was cooled to -72° C. (acetone/dry ice). Once at this temperature 4.62 mL (11.542 mmol) of a 2.5M hexane solution of n-butyllithium was added followed by 1.76 mL (12.592 mmol) of diisopropylamine. For formation of lithium diisopropyl amide the reaction solution was raised to 0° C. (ice bath) for 20 minutes and then lowered again to -72° C. To the cold reaction solution was added 2.0 g (10.493 mmol) of 2-trimethylsilyl-3-chlorothiophene as a 5 mL tetrahydrofuran solution over a 20 minute period. Reaction pot temperature was maintained below -70° C. to ensure regioselective deprotonation. After 30 minute reaction time carbon dioxide gas was slowly bubbled through the yellow solution. During the bubbling the reaction temperature was kept below -55° C. Total carbon dioxide treatment lasted 10 minutes. Following carbon dioxide addition the solution was gradually warmed to 0° C. at which point the reaction was quenched with 50 mL of 1N hydrochloric acid causing some gas evolution. On addition of the acidic solution the reaction was brought to room temperature. A 50 mL volume of brine was also added. The organic layer was separated and the aqueous was extracted with ethyl acetate (2×50 mL). The organic extracts were combined, washed with brine (1×50 mL), dried (sodium sulfate), filtered, and evaporated to 2.38 g of a white solid. Recrystallization of the crude product with heptane gave 1.67 g of pure title compound as small white needles, mp=206°-210° C.

Provenance & Evidence