تفاعل #1696289

معادلة التفاعل

hydrochloric acid

racemic 2-chloro-9,10-dihydro-9,10-methano-9-anthracenecarboxylic acid

(1S,2S)-(+)-pseudoephedrine

water

→

(9S,10S)-2-chloro-9,10-dihydro-9,10-methano-9-anthracene-carboxylic acid

المردود 81.0%

المذيبات

ethyl acetate

ethyl acetate

ethyl acetate

methanol

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةWith efficient agitation the mixture was warmed
2. 2
   درجة الحرارةto reflux
3. 3
   ترشيحAfter a minimum of 2 h the slurry was filtered
4. 4
   غسيلwashed with ethyl acetate
5. 5
   أخرىto yield
6. 6
   workup.WAITto reflux,held 30 minutes
7. 7
   درجة الحرارةcooled to 25 C
8. 8
   workup.WAITslowly, held 2 h
9. 9
   ترشيحfiltered
10. 10
    غسيلwashed with ethyl acetate
11. 11
    أخرىto provide further enriched salt (70 g; 0.16M; 79%; diastereomeric ratio 95:5, as determined by HPLC)
12. 12
    استخلاصextracted with diethyl ether (3×500 mL)
13. 13
    غسيلThe combined organic extracts were washed with brine,dried (MgSO4)
14. 14
    أخرىevaporated to an oil
15. 15
    workup.ADDITIONHexane was added
16. 16
    أخرىevaporated
17. 17
    أخرىto afford enantiomerically enriched acid (36 g; 0.13M; 98% recovery; enantiomeric ratio 99:1, as determined by HPLC) as a white solid
18. 18
    أخرىCrystallisation
19. 19
    workup.ADDITIONfrom a mixture of hexane (360 mL) and cyclohexane (720 mL)

الإجراء التجريبي

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).

المصدر