反应详情

温度

-45 °C

A solution of thieno[3,2-c]pyridine (5.0 g) in 75 mL THF (tetrahydrofuran) was cooled to −45° C. in a CH3CN/dry ice bath. n-Butyllithium (1.6M in hexanes) (35.0 ml) was added dropwise maintaining the internal temperature at or below −40° C. The addition took about 45 minutes. The reaction was stirred for 1 hour at −45° C. N-methyl-N-methoxyacetamide in 5 mL THF was added and as a result the reaction warmed to −30° C. The reaction was stirred at −45° C. for 1.5 hours. The reaction was quenched with saturated NH4Cl. The aqueous layer had a pH of about 8. The aqueous layer was extracted three times into EtOAc. The combined organic extracts were washed with brine and dried over MgSO4. The material was filtered, concentrated on a rotary evaporator and subjected to column chromatography (Biotage Horizon system, 120 g Analogix column, equilibrate with hexanes, elute with 50% EtOAc/hexanes). The most pure fractions were concentrated on a rotary evaporator and then triturated with Et2O to remove some color and collect a pale orange solid by filtration (2.667 g).

1. temperaturemaintaining the internal temperature at or below −40° C
2. additionThe addition
3. customas a result the reaction
4. temperaturewarmed to −30° C
5. stirringThe reaction was stirred at −45° C. for 1.5 hours
6. customThe reaction was quenched with saturated NH4Cl
7. extractionThe aqueous layer was extracted three times into EtOAc
8. washThe combined organic extracts were washed with brine
9. dry with materialdried over MgSO4
10. filtrationThe material was filtered
11. concentrationconcentrated on a rotary evaporator
12. washsubjected to column chromatography (Biotage Horizon system, 120 g Analogix column, equilibrate with hexanes, elute with 50% EtOAc/hexanes)
13. concentrationThe most pure fractions were concentrated on a rotary evaporator
14. customtriturated with Et2O
15. customto remove some color
16. customcollect a pale orange solid
17. filtrationby filtration (2.667 g)