反应详情

温度

25 °C

To a solution of racemic 2-chloro-9,10-dihydro-9,10-methano-9-anthracenecarboxylic acid (100 g; 0.37M) in ethyl acetate (1.5L) and methanol (75mL) was added solid (1S,2S)-(+)-pseudoephedrine (61.1 g; 0.37M). With efficient agitation the mixture was warmed to reflux, held for 30 minutes and slowly cooled to 25° C. After a minimum of 2 h the slurry was filtered and washed with ethyl acetate to yield enriched diastereomeric salt (88.6 g; 0.20M; 55%; diastereomeric ratio 80:20, as determined by HPLC). The enriched salt was slurried in 3% methanolic ethyl acetate (2.74 L),warmed to reflux,held 30 minutes,cooled to 25 C. slowly, held 2 h and then filtered and washed with ethyl acetate to provide further enriched salt (70 g; 0.16M; 79%; diastereomeric ratio 95:5, as determined by HPLC). Treatment of the further enriched salt with 5% methanolic ethyl acetate using the same procedure yielded highly enriched salt (60.0 g; 0.14M; 85%; diastereomeric ratio 99:1, as determined by HPLC). This salt (60 g; 0.14M) was added to water (1L) and the consequent suspension acidified to pH 2-3 with concentrated hydrochloric acid (15 mL) and then extracted with diethyl ether (3×500 mL). The combined organic extracts were washed with brine,dried (MgSO4) and evaporated to an oil. Hexane was added and evaporated to afford enantiomerically enriched acid (36 g; 0.13M; 98% recovery; enantiomeric ratio 99:1, as determined by HPLC) as a white solid. Crystallisation from a mixture of hexane (360 mL) and cyclohexane (720 mL) afforded enantiomerically pure (9S,10S)-2-chloro-9,10-dihydro-9,10-methano-9-anthracene-carboxylic acid as a white solid (30 g, 0.11 mol, 81%) mp 172°-173° C. αD =+101° (c=2.0,CHCl3).

1. temperatureWith efficient agitation the mixture was warmed
2. temperatureto reflux
3. filtrationAfter a minimum of 2 h the slurry was filtered
4. washwashed with ethyl acetate
5. customto yield
6. waitto reflux,held 30 minutes
7. temperaturecooled to 25 C
8. waitslowly, held 2 h
9. filtrationfiltered
10. washwashed with ethyl acetate
11. customto provide further enriched salt (70 g; 0.16M; 79%; diastereomeric ratio 95:5, as determined by HPLC)
12. extractionextracted with diethyl ether (3×500 mL)
13. washThe combined organic extracts were washed with brine,dried (MgSO4)
14. customevaporated to an oil
15. additionHexane was added
16. customevaporated
17. customto afford enantiomerically enriched acid (36 g; 0.13M; 98% recovery; enantiomeric ratio 99:1, as determined by HPLC) as a white solid
18. customCrystallisation
19. additionfrom a mixture of hexane (360 mL) and cyclohexane (720 mL)