反应详情

温度

20 °C

Add methylmagnesium chloride (0.66 L, 1.99 mol, 3M in THF) to a solution of (3R)-5-bromo-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3,4 dihydroisoquinoline (93.5 g, 0.24 mol) in diethyl ether (2.8 L) at −65° C. in an appropriate vessel. Then heat the reaction mixture to 20° C. over 2 hours and stir. After 16 hours, cool the mixture to 0° C. and quench the reaction with saturated aqueous ammonium chloride solution (2.5 L) and extract with ethyl acetate (2.5 L) and filter the mixture. Wash the combined organic extracts with brine (1 L), dry over anhydrous magnesium sulfate and concentrate under reduced pressure to give the crude title compound as an oil. Combine the oil with crude products from substantially same reactions run with 48 mmol and 229 mmol of [(3R)-5-bromo-3,4-dihydroisoquinolin-3-yl]methoxy-tert-butyl-dimethyl-silane and purify them by silica gel chromatography eluting with ethyl acetate in hexanes (gradient 5-65% ethyl acetate) to give the title compound (151 g, 0.41 mol). MS (m/z): 370.1 (M+1 (79Br)), 372.1 (M+1 (81Br)).

1. temperaturecool the mixture to 0° C.
2. customquench
3. customthe reaction with saturated aqueous ammonium chloride solution (2.5 L)
4. extractionextract with ethyl acetate (2.5 L)
5. filtrationfilter the mixture
6. washWash the combined organic extracts with brine (1 L)
7. dry with materialdry over anhydrous magnesium sulfate
8. concentrationconcentrate under reduced pressure
9. customto give the crude title compound as an oil
10. custompurify them by silica gel chromatography
11. washeluting with ethyl acetate in hexanes (gradient 5-65% ethyl acetate)