反应详情

A stirred solution of 1-bromo-2-cyclopropylmethoxy-4-fluoro-5-methoxy-benzene from example B.b10 (27.51 g; 0.10 mol) in dry tert.butylmethylether (500 mL) is cooled to −20° C. before addition of n-butyl lithium (1.6 M in hexane; 68.8 mL; 0.11 mol) via syringe. After complete addition stirring is continued for one hour. Neat 2-iso-propoxy-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane is added via syringe into the reaction mixture at −40° C. After 30 min the reaction is quenched with 1M citric acid (200 mL) at 0° C. and stirred for one hour at ambient temperature. The organic layer is separated. The aqueous layer is extracted with tert.-butylmethylether (100 mL). The combined organic layers are washed with brine (200 mL) dried over MgSO4 and filtered through a plug of neutral alumina containing 5 wt % of water. The product is completely eluted with several small portions of tert.-butylmethylether. The solvent is removed under reduced pressure. The crude is purified by short path distillation at 3×10−3 mbar (160° C.) to give the title compound as a colorless oil that solidifies at ambient temperature.

1. additionAfter complete addition
2. customAfter 30 min the reaction is quenched with 1M citric acid (200 mL) at 0° C.
3. stirringstirred for one hour at ambient temperature
4. customThe organic layer is separated
5. extractionThe aqueous layer is extracted with tert.-butylmethylether (100 mL)
6. washThe combined organic layers are washed with brine (200 mL)
7. dry with materialdried over MgSO4
8. filtrationfiltered through a plug of neutral alumina containing 5 wt % of water
9. washThe product is completely eluted with several small portions of tert.-butylmethylether
10. customThe solvent is removed under reduced pressure
11. distillationThe crude is purified by short path distillation at 3×10−3 mbar (160° C.)