Hydrochloric Acid → 3-BENZOYLTHIOPHENE

Temperature

-78 °C

The solution containing 0.937 mL (10 mmol) of 3-bromothiophene, 3 mL of tetrahydrofuran, and 8 mL of ether was cooled to −78° C. under N2. To the cooled solution was then added 4 mL of n-BuLi ([2.5] M in hexane) drop wise, while maintaining the reaction temperature below −70° C. The reaction solution turned to light yellow suspension. The suspension was allowed to stir 15 min at <−70° C. After 15 min, a solution containing 1.02 mL (10 mmol) of benzonitrile and 3 mL of tetrahydrofuran was added drop wise while maintaining the reaction temperature below −70° C. After the addition, the reaction suspension was allowed to stir 1 hr at −78° C. and slowly warmed to −10° C. over 2 hr. After 2 hr the reaction was stopped by adding 10 mL of H2O and 30 mL of 2N HCl. The aqueous solution was separated from the organic phase. The aqueous phase was washed with ether (2>20 mL). The washed aqueous solution was then heated to reflux for 2 hr. After 2 hr, the solution was cooled. To the cooled solution was added 30 mL of ether. The aqueous solution was removed. The organic solution was finally washed with brine, dried over MgSO4, and concentrated under reduced pressure. The concentrated sample was purified by flashy chromatography (hexane:ethyl acetate, from 4 to 6 % ethyl acetate over 16 column volume) to obtain 1.36 gm (72.3%) of a clear oil; 1H NMR 300 MHz (CDCl3) δ 7.93 (t, 1H), 7.83-7.86 (m, 2H), 7.26-7.61 (m, 5H).

1. temperaturewhile maintaining the reaction temperature below −70° C
2. waitAfter 15 min
3. additionwas added drop wise
4. temperaturewhile maintaining the reaction temperature below −70° C
5. additionAfter the addition
6. stirringto stir 1 hr at −78° C.
7. temperatureslowly warmed to −10° C. over 2 hr
8. waitAfter 2 hr the reaction was stopped
9. customThe aqueous solution was separated from the organic phase
10. washThe aqueous phase was washed with ether (2>20 mL)
11. temperatureThe washed aqueous solution was then heated
12. temperatureto reflux for 2 hr
13. waitAfter 2 hr
14. temperaturethe solution was cooled
15. additionTo the cooled solution was added 30 mL of ether
16. customThe aqueous solution was removed
17. washThe organic solution was finally washed with brine
18. dry with materialdried over MgSO4
19. concentrationconcentrated under reduced pressure
20. customThe concentrated sample was purified by flashy chromatography (hexane:ethyl acetate, from 4 to 6 % ethyl acetate over 16 column volume)

ORD record

ord-a8da424ff8f943a5b11b3732841e7375

Source dataset

uspto-grants-2008_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07435822B2