Carbon Dioxide → HCID 19035084, compound

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.

1. customis dry
2. temperatureAt this point the solution was cooled to -72° C. (acetone/dry ice)
3. additionOnce at this temperature 4.62 mL (11.542 mmol) of a 2.5M hexane solution of n-butyllithium was added
4. customlowered again to -72° C
5. customReaction pot temperature
6. temperaturewas maintained below -70° C.
7. customwas slowly bubbled through the yellow solution
8. customwas kept below -55° C
9. additionFollowing carbon dioxide addition the solution
10. temperaturewas gradually warmed to 0° C. at which
11. customwas quenched with 50 mL of 1N hydrochloric acid causing some gas evolution
12. additionOn addition of the acidic solution the reaction
13. customwas brought to room temperature
14. additionA 50 mL volume of brine was also added
15. customThe organic layer was separated
16. extractionthe aqueous was extracted with ethyl acetate (2×50 mL)
17. washwashed with brine (1×50 mL)
18. dry with materialdried (sodium sulfate)
19. filtrationfiltered
20. customevaporated to 2.38 g of a white solid
21. customRecrystallization of the crude product with heptane

ORD record

ord-48387daa4f974bbd851182c204d889d2

Source dataset

uspto-grants-1997_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05648502