反应详情

温度

-78 °C

3-Bromo-4-methylbenzoic acid (11.00 g, 51.2 mmol) was dissolved in anhydrous THF (150 ml) under argon in a 500 ml 3-necked round bottom flask fitted with two dropping funnels and argon inlet. The stirred solution was cooled to −78° C. and n-BuLi (1.6M in hexane, 60.7 ml, 97.0 mmol) was added drop wise from a dropping funnel (during 1 h). After completion of the addition, the solution was stirred at −78° C. for another 1 h. To this, B(OMe)3 (17.7 ml, 159.0 mmol) was added slowly from a second dropping funnel. The mixture was stirred 1 h at −78° C. and then warmed up to room temperature overnight. The solvent was evaporated under reduced pressure. The crude product was dissolved in ether and poured into aqueous HCl (1N). The mixture was extracted with ether (3×150 ml), and the combined organic layers were washed with brine, dried over anhydrous MgSO4, filtered, and evaporated to dryness. The crude product was purified using an ISCO system (220 g silica column, hexane/EtOAc gradient and later DCM/MeOH gradient). The impurities washed off in hexane/EtOAc and the pure product eluted in MeOH/DCM (5:95) solvent mixture to give 3.3 g (33% yield) of pure SKC-01-126. 1H NMR (400 MHz, Acetone-d6) δ 12.10 (br s, 1H), 8.16 (s, 1H), 7.90-7.63 (m, 1H), 7.11 (d, J=7.9 Hz, 1H), 2.42 (s, 3H).

1. customfitted with two dropping funnels and argon inlet
2. additionAfter completion of the addition
3. stirringThe mixture was stirred 1 h at −78° C.
4. temperaturewarmed up to room temperature overnight
5. customThe solvent was evaporated under reduced pressure
6. dissolutionThe crude product was dissolved in ether
7. additionpoured into aqueous HCl (1N)
8. extractionThe mixture was extracted with ether (3×150 ml)
9. washthe combined organic layers were washed with brine
10. dry with materialdried over anhydrous MgSO4
11. filtrationfiltered
12. customevaporated to dryness
13. customThe crude product was purified
14. washThe impurities washed off in hexane/EtOAc
15. washthe pure product eluted in MeOH/DCM (5:95) solvent mixture
16. customto give 3.3 g (33% yield) of pure SKC-01-126