反应详情

温度

-20 °C

Grignard reagent was made in a three necked reaction flask equipped with mechanical stirring, an intensive condenser and a pressure equilibrated funnel, using 4-bromo-fluorobenzene (55 ml, 500 mmol) and magnesium turnings (12.6 g, 520 mmol) in 500 ml absolute diethyl ether. The solution of grignard reagent was cooled to -20° C. and a solution of (-)-anhydroecgonine methyl ester (43 g, 233 mmol) in 200 ml absolute diethyl ether was added over 1/2 hour. The reaction was first stirred one hour at -20° C. and then 16 hours at room temperature and was finally quenched by addition of water (50 ml). The mixture was acidified by addition of hydrochloric acid (4M, 50 ml) and the aqueous phase was washed twice with diethyl ether. To the aqueous phase was added ammonium hydroxide (25%) to basic reaction and the resulting mixture was finally extracted three times with diethyl ether. After drying and concentration of the combined organic phase in vacuo, the crude product was subjected to column chromatography using diethyl ether+triethyl amine (5%) as eluent, yielding (1R,2S,3S)-2-(4'-fluoro-benzoyl)-3-(4-fluorophenyl)tropane, white crystals m.p. 178°-180° C. and (1R,2R,3S)-2-(4'-fluoro-benzoyl)-3-(4-fluorophenyl)tropane, white crystals m.p. 124°-140° C.

1. customequipped with mechanical stirring, an intensive condenser
2. custom16 hours at room temperature and was finally quenched by addition of water (50 ml)
3. additionThe mixture was acidified by addition of hydrochloric acid (4M, 50 ml)
4. washthe aqueous phase was washed twice with diethyl ether
5. additionTo the aqueous phase was added ammonium hydroxide (25%)
6. customto basic reaction
7. extractionthe resulting mixture was finally extracted three times with diethyl ether
8. customAfter drying